CRBN; TNF-α (IC50 = 13 nM)

(magnification, ×200).Pomalidomide has an IC50 of 13 nM and a 25 nM, respectively, for inhibiting lipopolysaccharide (LPS) stimulated TNF-alpha release in human PBMC and human whole blood. [1] Pomalidomide has an IC50 of 1 μM and inhibits T regulatory cell growth that is induced by IL-2. [2] Pomalidomide (6.4 nM–10 M) treatment causes an increase in IL-2 production in human peripheral blood T cells; this effect is marginally more pronounced in the CD4+ subset than in the CD8+ subset. Pomalidomide has a much greater ability to increase IL-2, IL-5, and IL-10 levels than CC-5013, but it has only a marginally greater ability to increase IFN-γ levels. Pomalidomide enhances SEE and Raji cells induced AP-1 transcriptional activity in Jurkat cells in a dose-dependent manner, with a maximal enhancement of 4-fold at 1 μM. [3] When Raji cells are exposed to different Pomalidomide concentrations (2.5–40 μg/mL) for 48 hours, cell proliferation and DNA synthesis are significantly reduced. In comparison to controls treated with the vehicle, there is a 40% reduction. [4]

In mice with severe combined immunodeficiency, pomalidomide improves rituximab's ability to treat B-cell lymphomas. In contrast to the 58 days of CC5013/rituximab treatment and the 45 days of rituximab nonotherapy, the mice with the combination of pomalidomide and rituximab have a median survival period of 74 days. Pomalidomide and rituximab have a synergistic effect, but this effect can be completely reversed by NK cell depletion, which lends support to the idea that one way Pomalidomide may increase rituximab antitumor activity is by promoting NK cell expansion. [4]

TNF-α inhibitory activity is measured in lipopolysacharide (LPS) stimulated PBMC. Pomalidomide is added to human PBMCs one hour before LPS (1 μg/mL) is added, and incubation is then continued for an additional 18 to 20 hours. The concentration of TNF-α is then measured in the supernatants using an ELISA after they are harvested. Nonlinear regression analysis is used to determine the amount of pomalidomide (IC50) required to reduce TNF-production by 50%. Similar to the PBMC assay, the human whole blood TNF-inhibition assay is carried out except that fresh human whole blood that has been heparinized is directly plated onto microtiter plates.

Pomalidomide (5 μg/mL) is applied to Lymphoma cell lines for 24 or 48 hours in order to measure cell apoptosis. Propidium iodine and FITC-labeled Annexin V are used to stain the cells. Fluorescence-activated cell sorter/FACStar Plus flow cytometer multicolor flow cytometric analysis is used to examine cell apoptosis. When cells show signs of early or late apoptosis (Annexin V positivity and propidium iodine negativity or positivity, respectively), they are considered to be apoptotic. The Lymphoma cell lines are exposed to Pomalidomide (2.5, 5, 10, 20, and 40 μg/mL) for 24 or 48 hours to measure cell proliferation. After adding 1 μCi of [3H]-thymidine per well (in a 96-well plate), the cells are given another 18 hours of incubation. The [3H]-thymidine uptake is then determined using an automated scintillation counter after cells are harvested using the Harvest system and placed into 96-well glass filters.

Mice: SCID mice aged six to eight weeks are used for this. All of the animals are injected with 1×106 Raji cells through their tail veins on day 0. The animals are divided into seven cohorts following 72 hours of tumor engraftment. The first cohort (group A) serves as the control and is not given any medication. Animals in Groups B and C were given either CC-5013 (0.5 mg/kg) or Pomalidomide (0.5 mg/kg) intravenously on Days +3, +4, +8, +9, +13, +14, +18, and +19. Rituximab or Trastuzumab (isotype control) monotherapy is administered to Groups D and E on Days +5, +10, +15, and +20 by tail vein injection at a dose of 10 mg/kg. Animals treated with Rituximab and CC-5013 (group E) or Pomalidomide (group G) make up groups F and G, respectively. Prior to each dose of Rituximab, IMiDs are administered intravenously for two consecutive days. Animals are monitored for 90 days after therapy is over. The study's primary outcome is survival, which is measured as the amount of time before limb paralysis sets in. Cervical dislocation is used to kill any animals that reach the end point or remain alive after three months of observation. To find any remaining disease, a pathologic examination of all organs is conducted, including the liver, lungs, and brain. Three different times, the experiments are repeated.
Rats: Three male CD-IGS rats in total are used. Pomalidomide is given as a single PO administration through the stomach cannula at a dose of 50 mg/kg (5 mL/kg) in a suspension formulation of 0.5% carboxymethylcellulose/0.25% Tween 80. Ten hours after dosing, microdialysate is collected in a cooling fraction collector set to 4°C at intervals of 25 minutes. Each sample's corrected concentration is multiplied by the sampling interval, in this case 25 minutes, and divided by the number of hours in a day to obtain the AUC. These values added together represented the overall AUC value for the given time frame. The concentration is plotted at each time point at the halfway point of each collection interval in order to create graphs. Within 12 hours of the specified time points, microdialysates are collected and analyzed for the presence of pomalidomide using a LC-MS/MS assay.

Absorption, Distribution and Excretion
Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses.
When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively.
Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L
Total body clearance = 7-10 L/hour
Pomalidomide has a mean apparent volume of distribution (Vd/F) between 62 and 138 L at steady state. Pomalidomide is distributed in semen of healthy subjects at a concentration of approximately 67% of plasma level at 4 hours post-dose (approximate Tmax) after 4 days of once-daily dosing at 2 mg. Human plasma protein binding ranges from 12% to 44% and is not concentration dependent. Pomalidomide is a substrate for P-glycoprotein (P-gp).
In patients with multiple myeloma who received Pomalyst 4 mg daily alone or in combination with dexamethasone, pomalidomide steady-state drug exposure was characterized by AUC(T) of 400 ng*h/mL and Cmax of 75 ng/mL. Following multiple doses, pomalidomide has an accumulation ratio of 27% to 31%.
Following a single oral administration of (14)C-pomalidomide (2 mg) to healthy subjects, approximately 73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with approximately 2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.
Pomalidomide has a mean total body clearance (CL/F) of 7-10 L/hr.
For more Absorption, Distribution and Excretion (Complete) data for Pomalidomide (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro.
In hepatocytes from rabbit and human, and in vivo in rat, monkey and human, pomalidomide was metabolized primarily via hydroxylation of the phthalimide ring (M14, M16 and M17) followed by glucuronidation (M12 and M13), hydrolysis of the glutarimide ring (M10 and M11), and hydrolysis of the phthalimide ring (M2). There were no unique or disproportionate metabolites observed in humans, compared to rats and monkeys.
Pomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. In vitro, CYP1A2 and CYP3A4 were identified as the primary enzymes involved in the CYP-mediated hydroxylation of pomalidomide, with additional minor contributions from CYP2C19 and CYP2D6.

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Biological Half-Life
Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours.
... the terminal half-lives of pomalidomide in animals ranged from mean values of 4 to 7 hours following an IV dose.
Pomalidomide is eliminated with a median plasma half-life of approximately 9.5 hours in healthy subjects and approximately 7.5 hours in patients with multiple myeloma.

Toxicity Summary
IDENTIFICATION AND USE: Pomalidomide is a solid yellow powder. Pomalidomide, a thalidomide analog, is an immunomodulatory agent with antineoplastic and antiangiogenic activity. It is used in patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. HUMAN EXPOSURE AND TOXICITY: Pomalidomide may cause fetal toxicity; it is a structural analog of thalidomide, a known human teratogen. Therefore, pomalidomide is contraindicated during pregnancy. Acute myelogenous leukemia (AML) has been reported in patients receiving pomalidomide as investigational therapy for uses other than multiple myeloma. Serious venous thromboembolic events have also been reported in patients receiving pomalidomide. Pomalidomide did not induce chromosomal aberrations in human peripheral blood lymphocytes. ANIMAL STUDIES: Chronic administration of pomalidomide was well tolerated in rats at doses of 50, 250 and 1000 mg/kg/day for 6 months. However, monkeys exhibited greater sensitivity to pomalidomide in the studies reported. The primary toxicities observed in monkeys were associated with the hematopoietic/lymphoreticular systems. In the 9-month study in monkeys with doses of 0.05, 0.1, and 1 mg/kg/day, morbidity and early euthanasia of 6 animals were observed at the dose of 1 mg/kg/day and were attributed to immunosuppressive effects (staphylococcal infection, decreased peripheral blood lymphocytes, chronic inflammation of the large intestine, lymphoid depletion of lymphoid tissues, and lymphoid hypocellularity of bone marrow) at high exposures of pomalidomide. These immunosuppressive effects resulted in early euthanasia of 4 monkeys due to poor health condition (watery stool, inappetence, reduced food intake, and weight loss); histopathological evaluation of these animals showed chronic inflammation of the large intestine and villous atrophy of the small intestine. Staphylococcal infection was observed in 4 monkeys; 3 of these animals responded to antibiotic treatment and 1 died without treatment. In addition, findings consistent with acute myelogenous leukemia led to euthanasia of 1 monkey; clinical observations and clinical pathology and/or bone marrow alterations observed in this animal were consistent with immunosuppression. Minimal or mild bile duct proliferation with associated increases in ALP and GGT were also observed at 1 mg/kg/day. Evaluation of recovery animals indicated that all treatment-related findings were reversible after 8 weeks of dosing cessation, except for proliferation of intrahepatic bile ducts observed in 1 animal in the 1 mg/kg/day group. Pomalidomide was teratogenic in rabbits when administered during the period of major organogenesis. Doses ranging from 10 to 250 mg/kg produced embryo-fetal developmental malformations and variations. Increased cardiac anomalies and skeletal malformations were seen at all dose levels. At 100 and 250 mg/kg/day, there were slight increases in post-implantation loss and slight decreases in fetal body weights. At 100 and/or 250 mg/kg/day, fetal malformations also included limb anomalies and associated skeletal deformities, moderate dilation of the lateral ventricle in the brain, abnormal placement of the right subclavian artery, absent intermediate lobe in the lungs, low-set kidney, altered liver morphology, incompletely or not ossified pelvis, an increased average for supernumerary thoracic ribs and a reduced average for ossified tarsals. Pomalidomide was also teratogenic in rats. Malformations such as the absence of urinary bladder, absence of thyroid gland, and fusion and misalignment of lumbar and thoracic vertebral elements (central and/or neural arches) sometimes associated with discontinuous and misshapen ribs were observed at all dosage levels (25, 250, and 1000 mg/kg/day). In a fertility and early embryonic development study in rats, pomalidomide was administered to male and female rats at doses of 25, 250, and 1000 mg/kg/day before, during, and after mating with animals at the same dose level. Uterine examination on Gestation Day 13 showed a decrease in mean number of viable embryos and an increase in postimplantation loss at all dose levels. Pomalidomide was not mutagenic in bacterial and mammalian mutation Ames assays, and did not induce micronuclei formation in polychromatic erythrocytes in bone marrow of rats administered doses up to 2000 mg/kg/day.

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Hepatotoxicity
Serum enzyme elevations occur in 1% to 2% of patients taking pomalidomide and are more frequent with higher doses. The enzyme abnormalities are usually mild and self-limited and rarely require drug discontinuation. In addition pomalidomide has been implicated in rare instances of clinically apparent, acute liver injury which can be severe and has been reported to lead to deaths from acute liver failure. However, few of these cases have been published and the clinical features, course and outcome of the typical case of liver injury from pomalidomide have not been defined. Both thalidomide and lenalidomide have been implicated in cases of clinically apparent acute liver injury and the presentation and course of injury is likely to be similar to that caused by pomalidomide. The latency to onset of cases of thalidomide associated liver injury is usually within 1 to 6 weeks of starting the antineoplastic agent. The clinical features vary greatly and can be hepatocellular or cholestatic. Cases of acute liver failure as well as vanishing bile duct syndrome with rapid marked cholestasis and hepatic failure have been described with thalidomide and lenalidomide. Immunoallergic features may be prominent and instances of Stevens Johnson syndrome and toxic epidermal necrolysis with and without liver injury have also been linked to therapy with thalidomide and its derivatives. In most cases, the injury resolves rapidly after therapy is stopped. Monitoring of liver tests at monthly intervals is recommended when using thalidomide and its derivatives, and stopping therapy early may play an important role in preventing severe and fatal outcomes.
Pomalidomide and the thalidomide derivatives have also been implicated in causing an increased risk of graft-vs-host disease after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) as well as after liver, kidney and heart transplantation. There appears to be cross reactivity to this complication among lenalidomide, pomalidomide and thalidomide. Therapy usually requires discontinuation of the antineoplastic agent as well as treatment with high doses of corticosteroids and tacrolimus or sirolimus. Furthermore, hepatic graft-vs-host disease can occasionally present with an acute hepatitis that resembles hepatocellular drug induced liver injury.
Reactivation of hepatitis B has been reported in patients receiving thalidomide, lenalidomide and pomalidomide, but generally only after HSCT and the role of these agents in causing reactivation is not always clear. Indeed, in studies of large numbers of patients treated for multiple myeloma the major risk factor for hepatitis B reactivation was found to be HSCT rather than the specific antineoplastic drugs being used. Indeed, lenalidomide therapy is associated with a reduced risk of reactivation in patients with HSCT (although dexamethasone, thalidomide and bortezomib were not), perhaps because of the immune enhancement typically caused by lenalidomide.
Likelihood score: D (possible cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of pomalidomide during breastfeeding. The manufacturer recommends that breastfeeding be discontinued during pomalidomide therapy
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
12-44% protein bound. It is not concentration dependent.

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Interactions
Pomalidomide is a substrate of the efflux transporter P-glycoprotein (P-gp); potent inhibitors or inducers of this transport protein may potentially alter pomalidomide exposure. Concomitant use of pomalidomide with potent inhibitors or inducers of P-gp should be avoided.
Metabolism of pomalidomide is mediated primarily by cytochrome P-450 (CYP) isoenzymes 1A2 and 3A4. Concomitant use of pomalidomide with potent inhibitors of CYP1A2 or CYP3A (e.g., ketoconazole) may increase exposure to pomalidomide and should be avoided. Conversely, concomitant use of pomalidomide with potent inducers of CYP1A2 (e.g., cigarette smoking) or CYP3A (e.g., rifampin) may decrease exposure to pomalidomide and also should be avoided. When the weak CYP3A inducer dexamethasone (20-40 mg once daily) was administered concomitantly with pomalidomide (4 mg once daily) in patients with multiple myeloma, pharmacokinetics of pomalidomide were unchanged. Pomalidomide does not inhibit or induce CYP isoenzymes in vitro.
Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. Our biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomide and pomalidomide.
Pomalidomide offers an alternative for patients with relapsed/refractory multiple myeloma who have exhausted treatment options with lenalidomide and bortezomib. Little is known about pomalidomide's potential for drug-drug interactions (DDIs); as pomalidomide clearance includes hydrolysis and cytochrome P450 (CYP450)-mediated hydroxylation, possible DDIs via CYP450 and drug-transporter proteins were investigated in vitro and in a clinical study. In vitro pomalidomide was neither an inducer nor inhibitor of CYP450, nor an inhibitor of transporter proteins P glycoprotein (P-gp), BCRP, OAT1, OAT3, OCT2, OATP1B1, and OATP1B3. Oxidative metabolism of pomalidomide was predominately mediated by CYP1A2 and CYP3A4, and pomalidomide was shown to be a P-gp substrate. In healthy males, co-administration of oral (4 mg) pomalidomide with ketoconazole (CYP3A/P-gp inhibitor) or carbamazepine (CYP3A/P-gp inducer) did not result in clinically relevant changes in pomalidomide exposure. Co-administration of pomalidomide with fluvoxamine (CYP1A2 inhibitor) in the presence of ketoconazole approximately doubled pomalidomide exposure. Pomalidomide appears to have low potential for clinically relevant DDI and is unlikely to affect the clinical exposure of other drugs. Avoid co-administration of strong CYP1A2 inhibitors unless medically necessary. Pomalidomide dose should be reduced by 50% if co-administered with strong CYP1A2 inhibitors and strong CYP3A/P-gp inhibitors.

[1]. Molecular mechanism of action of the immune-modulatory drugs, thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013 Apr;54(4):683-7.

[2]. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005 Aug 15;11(16):5984-92.

[3]. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32.

[4]. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models. PLoS One. 2013 Aug 5;8(8):e71754.

[5]. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015 Jun 18;22(6):755-63.

[6]. Tumour necrosis factor-α inhibits hepatic lipid deposition through GSK-3β/β-catenin signaling in juvenile turbot (Scophthalmus maximus L.). Gen Comp Endocrinol. 2016 Mar 1;228:1-8.

Therapeutic Uses
Angiogenesis Inhibitors; Immunologic Factors
Pomalyst is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified. /Included in US product label/
EXPL THER Pomalidomide /affected/ the regulation of fetal hemoglobin (HbF) making it a potential therapeutic agent for the treatment of non-malignant hematologic disorders such as sickle cell disease (SCD) and beta-thalassemia. In vitro pomalidomide was a more potent inducer of HbF than hydroxyurea (HU), the only treatment currently approved for SCD. Pomalidomide increased the expression of genes directing the production of HbF as well as gamma- and epsilon-globin gene transcription and expression during erythroid differentiation. In an in vivo knockout transgenic mouse model of SCD, pomalidomide (10 mg/kg; 5 QD/week x 8) stimulated erythropoiesis as indicated by bone marrow hyperplasia and increased extramedullary hematopoiesis, a trend toward higher reticulocytes and significantly higher red blood cell (RBC) levels. Pomalidomide significantly increased HbF expression with a trend toward higher gamma-globin chain A levels. The pomalidomide responder rate, defined as the percentage of animals that exceeded the maximum HbF and gamma-globin chain A levels in the vehicle group, reached 67% and 78% respectively. Among responders, pomalidomide induced a nearly 2-fold increase in HbF and the increase in gamma-globin chain A levels was significant and was similar to the approved HbF-inducing agent HU.

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Drug Warnings
/BOXED WARNING/ WARNING: EMBRYO-FETAL TOXICITY. Embryo-Fetal Toxicity: Pomalyst is contraindicated in pregnancy. Pomalyst is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting Pomalyst treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping Pomalyst treatment. Pomalyst is only available through a restricted distribution program called Pomalyst REMS.
/BOXED WARNING/ WARNING: VENOUS THROMBOEMBOLISM. Deep venous thrombosis (DVT) and pulmonary embolism (PE) occur in patients with multiple myeloma treated with Pomalyst. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient's underlying risk factors
Use of pomalidomide should be avoided in patients with serum aminotransferase (ALT and AST) concentrations exceeding 3 times the upper limit of normal (ULN) and bilirubin concentrations exceeding 2 mg/dL. Use of pomalidomide also should be avoided in patients with serum creatinine concentrations exceeding 3 mg/dL. Safety and efficacy have not been established in these patients.
Pomalidomide may cause fetal toxicity; pomalidomide is a structural analog of thalidomide, a known human teratogen, and teratogenic and other fetotoxic effects of pomalidomide (e.g., musculoskeletal anomalies and deformities; absence of internal organs, including bladder and thyroid; defects of internal organ systems, including cardiovascular, respiratory, renal, hepatic, and CNS abnormalities; increased fetal resorptions) have been demonstrated in animals. Therefore, pomalidomide is contraindicated in women who are pregnant.
For more Drug Warnings (Complete) data for Pomalidomide (21 total), please visit the HSDB record page.

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Pharmacodynamics
Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times).

C13H11N3O4

273.24

273.074

C, 57.14; H, 4.06; N, 15.38; O, 23.42

19171-19-8

Pomalidomide-d3;2093128-28-8;Pomalidomide-d5;1377838-49-7;Pomalidomide-d4;1416575-78-4

134780

white solid powder

1.6±0.1 g/cm3

582.9±45.0 °C at 760 mmHg

318.5 - 320.5°

306.3±28.7 °C

0.0±1.6 mmHg at 25°C

1.691

-0.74

2

5

1

20

504

0

O=C1C([H])(C([H])([H])C([H])([H])C(N1[H])=O)N1C(C2C([H])=C([H])C([H])=C(C=2C1=O)N([H])[H])=O

UVSMNLNDYGZFPF-UHFFFAOYSA-N

InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)

4-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione

CC4047; CC-4047; CC 4047; Pomalidomide. Brand name: Pomalyst

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 15mg/mL

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Solubility in Formulation 4: 10 mg/mL (36.60 mM) in 0.5% CMC-Na 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)