| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
Purity: =99.89%
| Targets |
CDK7-IN-3 is a highly selective, non-covalent inhibitor of cyclin-dependent kinase 7 (CDK7). CDK7 plays dual roles in cells: as the CDK-activating kinase (CAK), it activates CDK1, CDK2, CDK4, and CDK6, thereby regulating cell cycle progression; and as a component of the TFIIH transcription factor complex, it phosphorylates Ser5 and Ser7 of the C-terminal domain of RNA polymerase II, regulating transcription initiation and elongation. CDK7-IN-3 binds to CDK7 with a KD of 0.065-0.07 nM. The compound shows poor inhibition of CDK2 (Ki = 2600 nM), CDK9 (Ki = 960 nM), and CDK12 (Ki = 870 nM), demonstrating excellent selectivity for CDK7.
|
|---|---|
| ln Vitro |
SY-5609 (0.01-10000 nM; 72 hours) has strong antiproliferative effects on ovarian (OVA) and triple-negative breast cancer (TNBC) cells [1]. Apoptosis is induced by SY-5609 (100–500 nM; 48–72 hours) [1]. In HCC70 cells, SY-5609 (100–500 nM; 48 hours) causes G2/M cell cycle arrest [1]. Through CAK loss of function, SY-5609 (25–500 nM; 6-48 hours) suppresses CDK2 phosphorylation at Thr160 [1]. In the HCC70 cell line, SY-5609 (Compound 101; 126.4 pM-4 µM; 72 hours) has an EC50 of 5.6 nM [2].
CDK7-IN-3 is an orally active, highly selective, non-covalent CDK7 inhibitor with a KD of 0.065-0.07 nM. It shows poor inhibition of CDK2 (Ki=2600 nM), CDK9 (Ki=960 nM), and CDK12 (Ki=870 nM). The compound has potent antitumor activity and induces apoptosis. It inhibits cell proliferation in various cancer cell lines. CDK7-IN-3 is a promising anticancer agent targeting both cell cycle progression and transcription. |
| ln Vivo |
SY-5609 (2 mg/kg/day; oral; for 21 days) causes tumor regression throughout a 21-day dosage period [1]. Mice were orally treated 2 mg/kg SY-5609 daily, the plasma exposure was 261.28 ng h/mL, the Cmax was 50.67 ng/mL (103 nM), and the elimination half-life was 3.33 h[1].
In vivo, CDK7-IN-3 demonstrates potent antitumor activity in various preclinical models. As an orally bioavailable compound, it can be administered orally for convenient dosing. The compound has shown efficacy in inhibiting tumor growth in xenograft models. CDK7 inhibition leads to reduced phosphorylation of RNA polymerase II CTD and decreased expression of genes involved in cell cycle progression and survival. CDK7-IN-3 is being investigated as a potential therapeutic agent for various cancers, including those with CDK7 overexpression or dependence. |
| Enzyme Assay |
Kinase inhibition assays for CDK7-IN-3 are performed using recombinant CDK7/Cyclin H/MAT1 complex and appropriate peptide substrates. The assay typically employs a fluorescence-based or radiometric format to measure kinase activity. CDK7-IN-3 is incubated with the enzyme, substrate, and ATP in assay buffer for 30-60 minutes. The reaction is stopped and product formation is quantified. KD values are determined by surface plasmon resonance or isothermal titration calorimetry. Selectivity is assessed by screening CDK7-IN-3 against a panel of related kinases including CDK2, CDK9, and CDK12.
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HCC70, MDA-MB453, COV504, A2780, OVCAR3, CAOV3 Cell Tested Concentrations: 0.01-10000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Displayed strong anti-proliferative effect with IC50 of 1-6 nM . Apoptosis analysis[1] Cell Types: HCC70, MDA-MB-468, CAOV3 and OVCAR3 Cell Tested Concentrations: 100, 250, 500 nM Incubation Duration: 48 and 72 hrs (hours) Experimental Results: Induction of apoptosis. Cell cycle analysis[1] Cell Types: HCC70 Cell Tested Concentrations: 100, 250, 500 nM Incubation Duration: 48 hrs (hours) Experimental Results: Induced G2/M cell cycle arrest. Western Blot Analysis[1] Cell Types: HCC70 Cell Tested Concentrations: 25, 50, 100, 250, 500 nM Incubation Duration: 6, 24, 48 hrs (hours) Experimental Results: Inhibition of CDK2 phosphorylation at Thr160 via loss of CAK function 24 and 48 Hour. Cellular assays for CDK7 inhibition typically employ cancer cell lines. Cells are treated with varying concentrations of CDK7-IN-3 for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. RNA polymerase II CTD Ser5 phosphorylation is assessed by Western blot using phospho-specific antibodies. CDK7 target gene expression (e.g., MYC, MCL1, cyclin D1) is analyzed by qPCR. Cell cycle analysis is performed by propidium iodide staining. Apoptosis is evaluated by Annexin V/PI staining and caspase activity assays. The compound's effects on transcription and cell cycle progression are characterized. |
| Animal Protocol |
Animal/Disease Models: 6 to 8 weeks old HCC70 cell line Balb/c nude female mice [1]
Doses: 2 mg/kg Route of Administration: oral; daily; 21 days Experimental Results: Tumor induction over 21 days of dosing period subsided and was well tolerated. No tumor regrowth was observed until day 28. In vivo efficacy is evaluated in murine xenograft models using human cancer cell lines. Tumor-bearing mice are treated with CDK7-IN-3 orally at various doses (typically 10-50 mg/kg) daily or on a schedule. Tumor volumes are measured every 2-3 days. Pharmacodynamic markers such as RNA Pol II Ser5 phosphorylation and expression of CDK7 target genes are measured in tumor tissues. Body weight and clinical signs are monitored for tolerability assessment. The compound's oral bioavailability supports convenient dosing in preclinical studies. |
| ADME/Pharmacokinetics |
CDK7-IN-3 is orally bioavailable with good pharmacokinetic properties. The compound has molecular formula C23H26F3N6OP and molecular weight 490.46. It is a non-covalent CDK7 inhibitor with high selectivity. The compound is soluble in DMSO and should be stored at -20°C for long-term stability. For in vivo studies, appropriate oral formulations would be required.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies for CDK7-IN-3 are ongoing as part of clinical development. As a CDK7 inhibitor targeting both cell cycle and transcription, potential toxicities may include myelosuppression, gastrointestinal effects, and other on-target effects. The compound has been evaluated in preclinical models with acceptable tolerability. Standard safety pharmacology, genotoxicity, and repeated-dose toxicity studies would be required for regulatory approval.
|
| References | |
| Additional Infomation |
SY-5609, a CDK7 inhibitor, is a highly bioavailable, selective cyclin-dependent kinase 7 (CDK7) inhibitor with potential antitumor activity. After oral administration, SY-5609 selectively targets, binds to, and inhibits CDK7 activity, thereby suppressing CDK7-mediated signaling. Specifically, CDK7 inhibition prevents phosphorylation of the C-terminal domain (CTD) of RNA polymerase II, thus blocking the transcription of key oncogenes. Furthermore, it also prevents phosphorylation of cyclin kinases CDK1, 2, 4, and 6, thereby interfering with uncontrolled cell cycle progression. In summary, this may induce apoptosis, lead to cell cycle arrest, inhibit DNA damage repair, and suppress tumor cell proliferation in certain cancers that rely on CDK7-mediated transcriptional regulation and signaling. CDK7 is a serine/threonine kinase that plays a role in controlling cell cycle progression and transcriptional regulation, and promotes the expression of key oncogenes such as c-Myc and β-catenin through phosphorylation of RNA polymerase II.
CDK7-IN-3 is a novel, selective, non-covalent and orally bioavailable CDK7 inhibitor with anticancer activity. It is also known as SY-5609. CDK7 has emerged as an exciting target in oncology due to its dual role in cell cycle regulation and transcription. The compound is being developed for the treatment of various cancers, including those with CDK7 dependence or overexpression. |
| Molecular Formula |
C23H26F3N6OP
|
|---|---|
| Molecular Weight |
490.4611
|
| Exact Mass |
490.185
|
| CAS # |
2417302-07-7
|
| PubChem CID |
146662729
|
| Appearance |
White to light yellow solid powder
|
| LogP |
2.7
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
34
|
| Complexity |
838
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
P(C([H])([H])[H])(C([H])([H])[H])(C1=C(C#N)C([H])=C([H])C2=C1N([H])C([H])=C2C1C(C(F)(F)F)=C([H])N=C(N=1)N([H])[C@]1([H])C([H])([H])N([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])[H])=O
|
| InChi Key |
JDJOUBVVSQDIRC-AWEZNQCLSA-N
|
| InChi Code |
InChI=1S/C23H26F3N6OP/c1-22(2)8-7-14(10-30-22)31-21-29-12-17(23(24,25)26)18(32-21)16-11-28-19-15(16)6-5-13(9-27)20(19)34(3,4)33/h5-6,11-12,14,28,30H,7-8,10H2,1-4H3,(H,29,31,32)/t14-/m0/s1
|
| Chemical Name |
7-dimethylphosphoryl-3-[2-[[(3S)-6,6-dimethylpiperidin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-1H-indole-6-carbonitrile
|
| Synonyms |
SY 5609SY-5609 SY5609
|
| 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 (e.g. under nitrogen), 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) |
DMSO : ~40 mg/mL (~81.56 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 4 mg/mL (8.16 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 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. Solubility in Formulation 2: ≥ 4 mg/mL (8.16 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 40.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.10 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0389 mL | 10.1945 mL | 20.3890 mL | |
| 5 mM | 0.4078 mL | 2.0389 mL | 4.0778 mL | |
| 10 mM | 0.2039 mL | 1.0195 mL | 2.0389 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA