| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
CDK7
Mevociclib targets cyclin-dependent kinase 7 (CDK7), a serine/threonine kinase that plays a crucial role in cell proliferation and transcriptional regulation. It is a covalent/irreversible inhibitor with a Ki of 17.4 nM. It displays high selectivity against all other CDKs, including CDK2, CDK9, and CDK12 (IC₅₀ >2 µM). |
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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].
In vitro, Mevociclib inhibits CDK7 with an IC₅₀ of 20 nM for the CDK7/CycH/MAT1 complex. At nanomolar concentrations, it inhibits the growth of numerous cancer cell types. It reduces MCL1 protein levels and shows enhanced susceptibility in cancer cells expressing less BCL2L1 (BCL-XL). It exhibits activity in colorectal, lung, breast, and ovarian cancer cells. |
| 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].
In vivo, Mevociclib (20 mg/kg; iv; biw; for 35 days) suppresses tumor growth in a TNBC xenograft model. It shows significant antitumor effects in several AML xenograft models. When combined with the BCL2 inhibitor venetoclax, SY-1365-induced growth inhibition is amplified. Xenograft models of ovarian cancer also show antitumor activity. |
| Enzyme Assay |
The in vitro kinase assay for Mevociclib measures the inhibition of CDK7 kinase activity. Recombinant CDK7/CycH/MAT1 complex is incubated with the compound and a peptide substrate in the presence of ATP. The phosphorylation of the substrate is quantified. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays are performed using various cancer cell lines, including colorectal, lung, breast, ovarian, and AML cells. Cells are treated with Mevociclib, and cell proliferation is measured using assays such as CellTiter-Glo. Apoptosis is assessed by measuring caspase activation or Annexin V staining. The compound's effects on gene expression are analyzed by RNA-seq.
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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. In vivo animal experiments for Mevociclib have been conducted in mouse xenograft models, including HCC70 (TNBC) and AML models. Animals are administered the compound intravenously at 20 mg/kg twice weekly for 35 days. Tumor volume is measured, and pharmacodynamic markers such as CDK7 target engagement and downstream effects are assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mevociclib have been characterized in preclinical species. It is administered intravenously and achieves sufficient plasma concentrations to exert its pharmacological effects. Detailed PK parameters such as half-life, clearance, and volume of distribution are determined from plasma concentration-time profiles.
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| Toxicity/Toxicokinetics |
Toxicological data for Mevociclib are limited as it is an investigational compound. In standard preclinical safety assessments, it would be evaluated for potential off-target effects and general toxicity. The compound is intended for research use only and not for therapeutic use in humans.
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| References | |
| Additional Infomation |
Mevociclib (SY-1365) is a selective CDK7 inhibitor. Mevociclib exhibits anti-proliferative and pro-apoptotic effects in solid tumor cell lines. Mevociclib possesses antitumor activity against hematologic malignancies and various aggressive solid tumors. Mevociclib is a selective cyclin-dependent kinase 7 (CDK7) inhibitor with potential antitumor activity. After administration, SY-1365 binds to CDK7 and inhibits its activity, thereby suppressing CDK7-mediated signal transduction pathways. This can inhibit the growth of CDK7-overexpressing tumor cells. CDK7 is a serine/threonine kinase that plays a crucial role in cell proliferation; CDK7 is overexpressed in various tumor cell types.
Mevociclib (SY-1365) is a first-in-class selective CDK7 inhibitor that has been investigated for the treatment of transcriptionally driven cancers. It has demonstrated anti-proliferative and pro-apoptotic effects in solid tumor cell lines and antitumor activity against hematologic malignancies. It has been studied in phase 1 clinical trials but is not approved for clinical use. |
| 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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| PubChem CID |
118426108
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
42
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| Complexity |
952
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| Defined Atom Stereocenter Count |
2
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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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