| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
Cobomarsen (10 μM; 48-96 hours) inhibits the growth of U2932, OCI-LY3, and RCK8 cells and causes them to undergo apoptosis [2]. In cell lines overexpressing miR-155, cobomarsen (10 μM; 72 hours) dramatically boosts the expression of four direct targets [1]. In MF and HTLV-1+ CTCL cells, cobomarsen (10 μM; 12 days) decreases cell growth and causes death [1]. In primary human activated T cells or MF cell lines, cobomarsen (10-50 μM; 7 days) decreases the phosphorylation of downstream signaling proteins AKT, ERK1/2, and STAT-3 [1].
|
|---|---|
| ln Vivo |
Cobomarsen (1 mg/kg; intravenously on days 0, 2, 4, and 7) suppresses tumor growth in mice carrying U2932 cell xenografts [2].
|
| Cell Assay |
Cell proliferation assay[2]
Cell Types: U2932, OCI-LY3 and RCK8 Cell Tested Concentrations: 10 μM Incubation Duration: 48, 72, 96 hrs (hours) Experimental Results: Concentration-dependent inhibition of cellular phosphorylation. Apoptosis analysis[2] Cell Types: U2932, OCI-LY3 and RCK8 Cell Tested Concentrations: 10 μM Incubation Duration: 96 hrs (hours) Experimental Results: Significant induction of late apoptosis in all cell lines. |
| Animal Protocol |
Animal/Disease Models: Five to sixweeks old female NSG mice injected with U2932 cells.
Doses: 1 mg/kg. Route of Administration: intravenous (iv) (iv)injection on days 0, 2, 4, and 7. Experimental Results: Tumor growth diminished most Dramatically on days 7 and 10. With. |
| References |
|
| Additional Infomation |
Cobomarsen is under investigation in clinical trial NCT02580552 (Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL).
Cobomarsen is a locked nucleic acid (LNA)-based oligonucleotide inhibitor of microRNA (miRNA) 155 (miR-155), with potential antineoplastic activity. Upon administration, cobomarsen targets, binds to and inhibits miR-155. This silences miR-155 and prevents the translation of certain tumor promoting genes, which leads to the induction of cancer cell apoptosis and the inhibition of tumor cell growth. miR-155, an oncogenic single-stranded, non-coding RNA that is critical to the regulation of gene expression, is overexpressed in certain tumor cell types. Up-regulation of miR-155 plays a key role in increased tumor cell proliferation and survival. The LNA is an RNA analog in which the ribose ring is locked in a particular confirmation that increases stability. Compared to the unmodified oligonucleotide, the LNA-modified oligonucleotide shows increased affinity for its target miR-155. |
| Molecular Formula |
C148H177N52O77P13S13
|
|---|---|
| Molecular Weight |
4735.80
|
| Exact Mass |
4733.452
|
| CAS # |
1848257-52-2
|
| PubChem CID |
126480232
|
| Appearance |
White to off-white solid powder
|
| LogP |
-10.4
|
| Hydrogen Bond Donor Count |
31
|
| Hydrogen Bond Acceptor Count |
114
|
| Rotatable Bond Count |
80
|
| Heavy Atom Count |
303
|
| Complexity |
13400
|
| Defined Atom Stereocenter Count |
51
|
| SMILES |
S=P(O)(OC[C@@]12CO[C@@]([H])([C@H](N3C(NC(C(C)=C3)=O)=O)O1)[C@@H]2OP(O)(OC[C@@]12CO[C@@]([H])([C@H](N3C=NC4=C(N)N=CN=C34)O1)[C@@H]2O)=S)O[C@H]1[C@]2([H])[C@H](N3C(NC(C(C)=C3)=O)=O)O[C@@]1(COP(O)(O[C@H]1[C@]3([H])[C@H](N4C=NC5=C(N)N=CN=C45)O[C@@]1(COP(O)(O[C@H]1C[C@H](N4C(N=C(C=C4)N)=O)O[C@@H]1COP(O)(O[C@H]1[C@]4([H])[C@H](N5C=NC6C(NC(N)=NC5=6)=O)O[C@@]1(COP(O)(O[C@H]1C[C@H](N5C=NC6=C(N)N=CN=C56)O[C@@H]1COP(O)(O[C@H]1[C@]5([H])[C@H](N6C(NC(C(C)=C6)=O)=O)O[C@@]1(COP(O)(O[C@H]1[C@]6([H])[C@H](N7C(NC(C(C)=C7)=O)=O)O[C@@]1(COP(O)(O[C@H]1C[C@H](N7C=NC8=C(N)N=CN=C78)O[C@@H]1COP(O)(O[C@H]1C[C@H](N7C=NC8C(NC(N)=NC7=8)=O)O[C@@H]1COP(O)(O[C@H]1[C@]7([H])[C@H](N8C(N=C(C(C)=C8)N)=O)O[C@@]1(COP(O)(O[C@H]1C[C@H](N8C=NC9=C(N)N=CN=C89)O[C@@H]1COP(O)(O[C@H]1[C@]8([H])[C@H](N9C(N=C(C(C)=C9)N)=O)O[C@@]1(CO)CO8)=S)=S)CO7)=S)=S)=S)CO6)=S)CO5)=S)=S)CO4)=S)=S)CO3)=S)CO2
|
| InChi Key |
NNUHKSNTEOVPHV-XHZCTNOISA-N
|
| InChi Code |
InChI=1S/C148H177N52O77P13S13/c1-55-14-188(134(210)177-102(55)150)123-85-94(140(25-201,256-123)26-230-85)270-279(217,292)239-23-69-64(11-74(253-69)195-49-170-78-105(153)160-44-165-110(78)195)268-284(222,297)244-36-142-28-231-86(124(258-142)189-15-56(2)103(151)178-135(189)211)95(142)271-280(218,293)241-22-68-62(13-76(255-68)197-51-174-82-114(197)179-131(157)181-120(82)207)265-278(216,291)238-20-67-63(10-73(252-67)194-48-169-77-104(152)159-43-164-109(77)194)267-285(223,298)245-37-143-29-233-88(126(259-143)191-17-58(4)117(204)184-137(191)213)97(143)275-288(226,301)248-40-144-30-232-87(125(260-144)190-16-57(3)116(203)183-136(190)212)96(144)272-281(219,294)242-24-70-65(12-75(254-70)196-50-171-79-106(154)161-45-166-111(79)196)269-286(224,299)246-38-147-33-237-92(130(264-147)200-54-175-83-115(200)180-132(158)182-121(83)208)100(147)273-282(220,295)240-21-66-61(9-72(251-66)187-8-7-71(149)176-133(187)209)266-283(221,296)247-39-148-34-236-91(129(263-148)199-53-173-81-108(156)163-47-168-113(81)199)101(148)277-290(228,303)250-42-146-32-235-90(128(262-146)193-19-60(6)119(206)186-139(193)215)99(146)276-289(227,302)249-41-145-31-234-89(127(261-145)192-18-59(5)118(205)185-138(192)214)98(145)274-287(225,300)243-35-141-27-229-84(93(141)202)122(257-141)198-52-172-80-107(155)162-46-167-112(80)198/h7-8,14-19,43-54,61-70,72-76,84-101,122-130,201-202H,9-13,20-42H2,1-6H3,(H,216,291)(H,217,292)(H,218,293)(H,219,294)(H,220,295)(H,221,296)(H,222,297)(H,223,298)(H,224,299)(H,225,300)(H,226,301)(H,227,302)(H,228,303)(H2,149,176,209)(H2,150,177,210)(H2,151,178,211)(H2,152,159,164)(H2,153,160,165)(H2,154,161,166)(H2,155,162,167)(H2,156,163,168)(H,183,203,212)(H,184,204,213)(H,185,205,214)(H,186,206,215)(H3,157,179,181,207)(H3,158,180,182,208)/t61-,62-,63-,64-,65-,66+,67+,68+,69+,70+,72+,73+,74+,75+,76+,84+,85+,86+,87+,88+,89+,90+,91+,92+,93-,94-,95-,96-,97-,98-,99-,100-,101-,122+,123+,124+,125+,126+,127+,128+,129+,130+,140-,141+,142+,143+,144+,145+,146+,147+,148+,278?,279?,280?,281?,282?,283?,284?,285?,286?,287?,288?,289?,290?/m0/s1
|
| Chemical Name |
1-[(1R,3R,4R,7S)-1-[[[(1R,3R,4R,7S)-1-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(1R,3R,4R,7S)-3-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-1-[[[(2R,3S,5R)-2-[[[(1S,3R,4R,7S)-3-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-3-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-7-[[(2R,3S,5R)-3-[[(1R,3R,4R,7S)-3-(2-amino-6-oxo-1H-purin-9-yl)-7-[[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-[[(1R,3R,4R,7S)-3-(6-aminopurin-9-yl)-7-[[(1R,3R,4R,7S)-7-[[(1R,3R,4R,7S)-7-[[(1R,3R,4R,7S)-3-(6-aminopurin-9-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-3-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-3-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-methylpyrimidine-2,4-dione
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~21.11 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2112 mL | 1.0558 mL | 2.1116 mL | |
| 5 mM | 0.0422 mL | 0.2112 mL | 0.4223 mL | |
| 10 mM | 0.0211 mL | 0.1056 mL | 0.2112 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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