| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Emavusertib (CA-4948) is a first-in-class, orally bioactive and highly potent IRAK4/FLT3 inhibtor (IC50 of < 50 nM) with anticancer activity. CA4948 is currently undergoing testing in a Phase 1 trial in patients with non-Hodgkin's lymphoma and in a Phase 1 trial in patients with acute myeloid leukemia and myelodysplastic syndromes.
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| ln Vitro |
When compared to IRAK-1, emavusertib (CA-4948) exhibits an over 500-fold selectivity for IRAK-4. With an IC50 of less than 250 nM, emavusertib decreases the release of TNF-α, IL-1β, IL-6, and IL-8 from TLR-stimulated THP-1 cells. Because emavusertib inhibits the receptor-type casein inhibitor FLT3, it still has binding antiproliferative action [1]. Emavusertib binds to IRAK-4 more strongly than it does to IRAK 1, 2, and 3. In marginal zone quiescent zone (MZL) cell lines, emavusertib (10 μM, 72 h) decreases the total number of proliferating cells and increases sub-G0 fractional motility [3]. Emavusertib (10 μM, 72 h) exhibits efficacy greater than 350 times [3]. can cause a noticeable rise in the quantity of MZL cells, particularly when taken in conjunction with Ibrutinib [3].
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| ln Vivo |
In animal models, emavusertib (CA-4948) has shown anticancer efficacy against cancers with mutations in the MyD88 gene. In FLT3 wild-type and FLT3 mutant acute myeloid leukemia (AML) animal models, emavusertib exhibits antileukemic action [1]. Emavusertib can decrease tumor growth in mice when given orally, once daily, for 14 days at a dose of 25–150 mg/kg [3].
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| Animal Protocol |
Animal/Disease Models: Mice bearing OCI-LY10 tumors[3]
Doses: 25, 50, or 150 mg/kg (one time/day), 12.5, 25, or 50 mg/kg (twice (two times) daily) Route of Administration: Orally, one time/day or twice (two times) daily , for 14 days Experimental Results: Induced tumor growth inhibition. Emavusertib administered as a twice-daily divided dose was equivalent to the corresponding once-daily dose with regards to antitumor activity, ie, 12.5 mg/kg BID versus 25 mg/kg QD. |
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| Additional Infomation |
Emavusertib is an orally bioavailable, reversible inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), with potential antineoplastic, immunomodulating and anti-inflammatory activities. Upon oral administration, emavusertib targets, binds to, and blocks the kinase activity of IRAK4. This inhibits IRAK4-mediated signaling, prevents the activation of IRAK4-mediated nuclear factor-kappa B (NF-kB) signaling and decreases the expression of inflammatory cytokines and certain pro-survival factors. This inhibits proliferation of IRAK4-overactivated tumor cells, which are found in cells harboring MYD88 activating mutations or those with overactivated toll-like receptor (TLR) pathways. In addition, CA-4948 may inhibit inflammation and immune-mediated cell destruction in inflammatory and auto-immune diseases where TLR or interleukin 1 receptor (IL-1R) signaling is overactivated and MYD88 is dysregulated. IRAK4, a serine/threonine-protein kinase that plays a key role in both the TLR and IL-1R signaling pathways, is activated though the adaptor protein MYD88 and links the TLR and IL-1R signaling pathway to the NF-kB pathway.
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| Molecular Formula |
C24H25N7O5
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|---|---|
| Molecular Weight |
491.499204397202
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| Exact Mass |
491.19
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| Elemental Analysis |
C, 58.65; H, 5.13; N, 19.95; O, 16.28
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| CAS # |
1801344-14-8
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| Related CAS # |
Emavusertib hydrochloride;2376399-42-5
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| PubChem CID |
118224491
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
1.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
773
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=NC=CC(=C1)C2=NC(=CO2)C(=O)NC3=CC4=C(N=C3N5CC[C@H](C5)O)N=C(O4)N6CCOCC6
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| InChi Key |
SJHNWSAWWOAWJH-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C24H25N7O5/c1-14-10-15(2-4-25-14)23-27-18(13-35-23)22(33)26-17-11-19-20(28-21(17)31-5-3-16(32)12-31)29-24(36-19)30-6-8-34-9-7-30/h2,4,10-11,13,16,32H,3,5-9,12H2,1H3,(H,26,33)/t16-/m1/s1
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| Chemical Name |
(R)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide
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| Synonyms |
CA4948 Emavusertib CA 4948 CA-4948
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~101.73 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.23 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 20.8 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. Solubility in Formulation 2: 2.08 mg/mL (4.23 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0346 mL | 10.1729 mL | 20.3459 mL | |
| 5 mM | 0.4069 mL | 2.0346 mL | 4.0692 mL | |
| 10 mM | 0.2035 mL | 1.0173 mL | 2.0346 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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