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Purity: ≥98%
Mevociclib (formerly SY-1365; SY1365) is a novel, potent, highly selective and covalent/irreversible inhibitor of CDK7 (Cyclin-dependent kinase 7) with anticancer activity. SY-1365 has the potential to be used therapeutically for solid and hematological tumors. At nanomolar concentrations, SY-1365 inhibited the growth of numerous cancer types' cells in vitro. MCL1 protein levels were reduced by SY-1365 treatment, and it was discovered that cancer cells that expressed less BCL2L1 (BCL-XL) were more susceptible to SY-1365. Acute myeloid leukemia (AML) cell lines showed different transcriptional alterations after treatment with other transcriptional inhibitors. As a single agent, SY-1365 showed significant antitumor effects in several AML xenograft models; when combined with the BCL2 inhibitor venetoclax, SY-1365-induced growth inhibition was amplified. Additionally, xenograft models of ovarian cancer showed antitumor activity, indicating that SY-1365 may be investigated in the clinic for solid and hematologic tumors alike. Our results validate CDK7 targeting as a novel therapeutic strategy for transcriptionally driven cancers.
| Targets |
CDK7
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|---|---|
| ln Vitro |
Mevociclib has an IC50 of 20 nM for CDK7/CycH/MAT1 inhibition[2]. Mevociclib, a highly selective covalent CDK7, has no effect on non-growing cells but causes cell cooling in albino cells [2]. Mevociclib exhibits action in colorectal, lung, breast, and ovarian cancer cells; these cells display low nM EC50 and fast cellular fluorescence induction [2].
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| ln Vivo |
In an in vivo TNBC tumor model, mevociclib (20 mg/kg; iv; biw; for 35 days) suppresses growth [2]. A distinct transcriptional signature is induced by mevociclib [2].
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| Animal Protocol |
Animal/Disease Models: Mouse, HCC70 xenograft model [2]
Doses: 20 mg/kg Route of Administration: intravenous (iv) (iv)injection, twice a week for 35 days Experimental Results: Inhibition of tumor volume in vivo. |
| References |
[1]. Hu S, et al. Discovery and characterization of SY-1365, a selective, covalent inhibitor of CDK7. Cancer Res. 2019 May 7.
[2]. Shanhu Hu, et al. SY-1365, a potent and selective CDK7 inhibitor, exhibits promising anti-tumor activity in multiple preclinical models of aggressive solid tumors. |
| Molecular Formula |
C31H35CLN8O2
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|---|---|
| Molecular Weight |
587.115004777908
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| Exact Mass |
586.26
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| Elemental Analysis |
C, 63.42; H, 6.01; Cl, 6.04; N, 19.09; O, 5.45
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| CAS # |
1816989-16-8
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| Related CAS # |
1816989-16-8;Mevociclib mesylate; Mevociclib HCl;
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| Appearance |
Solid powder
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| SMILES |
C[C@@]1(CCC[C@H](C1)NC2=NC=C(C(=N2)C3=CNC4=CC=CC=C43)Cl)NC(=O)C5=NC=C(C=C5)NC(=O)/C=C/CN(C)C
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| InChi Key |
SCJNYBYSTCRPAO-LXBQGUBHSA-N
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| InChi Code |
InChI=1S/C31H35ClN8O2/c1-31(39-29(42)26-13-12-21(17-33-26)36-27(41)11-7-15-40(2)3)14-6-8-20(16-31)37-30-35-19-24(32)28(38-30)23-18-34-25-10-5-4-9-22(23)25/h4-5,7,9-13,17-20,34H,6,8,14-16H2,1-3H3,(H,36,41)(H,39,42)(H,35,37,38)/b11-7+/t20-,31+/m1/s1
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| Chemical Name |
N-[(1S,3R)-3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]-1-methylcyclohexyl]-5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]pyridine-2-carboxamide
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| Synonyms |
SY-1365; SY 1365; SY1365
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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: ~125 mg/mL (~212.9 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.54 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 (3.54 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7032 mL | 8.5161 mL | 17.0323 mL | |
| 5 mM | 0.3406 mL | 1.7032 mL | 3.4065 mL | |
| 10 mM | 0.1703 mL | 0.8516 mL | 1.7032 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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