CDK7-IN-34
CDK7-IN-34 is an orally active and selective CDK7 inhibitor with an IC50 of 3 nM. CDK7-IN-34 targets and inhibits the CDK7/cyclin H/MAT1 (CAK) complex, reducing the phosphorylation levels of downstream CDK1/2 and RNA polymerase II CTD and downregulating c-Myc expression, ultimately inducing tumor cell cycle arrest and transcriptional suppression. CDK7-IN-34 can be used for research on triple-negative breast cancer and colorectal cancer.
For research use only. We do not sell to patients.
- Formula: C29H43N7O2
- Molecular Weight:521.70
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Size
Price
Stock
Quantity
Amount: USD 0.00
Please select quantity
or
or
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
All DNA/RNA Synthesis Isoforms
More
Biological Activity
Description
CDK7-IN-34 is an orally active and selective CDK7 inhibitor with an IC50 of 3 nM. CDK7-IN-34 targets and inhibits the CDK7/cyclin H/MAT1 (CAK) complex, reducing the phosphorylation levels of downstream CDK1/2 and RNA polymerase II CTD and downregulating c-Myc expression, ultimately inducing tumor cell cycle arrest and transcriptional suppression. CDK7-IN-34 can be used for research on triple-negative breast cancer and colorectal cancer[1].
IC50 & Target
[1]|
CDK7/Mat1/cyclinH1 3 nM (IC50) |
CDK2/cyclin E1 3910 nM (IC50) |
cdk6/cyclin D3 565.4 nM (IC50) |
DNA Polymerase |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | EC50 |
0.34 μM
|
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| BT-549 | EC50 |
0.71 μM
|
Antiproliferative activity against human BT-549 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human BT-549 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| HCC70 | EC50 |
0.22 μM
|
Antiproliferative activity against human HCC70 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human HCC70 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| HCT-116 | EC50 |
0.13 μM
|
Antiproliferative activity against human HCT116 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human HCT116 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| LNCaP | EC50 |
0.56 μM
|
Antiproliferative activity against human LNCap cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human LNCap cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| OVCAR-3 | EC50 |
0.66 μM
|
Antiproliferative activity against human OVCAR3 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human OVCAR3 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| MV4-11 | EC50 |
0.16 μM
|
Antiproliferative activity against human MV-4-11 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
Antiproliferative activity against human MV-4-11 cells assessed as viability reduction incubated 120 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| NCM460 | EC50 |
1.61 μM
|
Cytotoxicity against human NCM-460 cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
Cytotoxicity against human NCM-460 cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| MCF-10A | EC50 |
0.94 μM
|
Cytotoxicity against human MCF-10A cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
Cytotoxicity against human MCF-10A cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
| RWPE-1 | EC50 |
2.00 μM
|
Cytotoxicity against human RWPE-1 cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
Cytotoxicity against human RWPE-1 cells assessed as viability reduction incubated 72 hrs by CCK-8 assay.
|
acs.jmedchem.6c01660 |
In Vitro
Anti-cancerCell Cycle RegulationOthers
Anti-cancer
CDK7-IN-34 (compound I-23) (120 h) exhibits potent anti-cell proliferation activity in MDA-MB-231, BT-549, HCC70, HCT116, LNCap, OVCAR3, and MV-4-11 tumor cells, with EC50 values of 0.34, 0.71, 0.22, 0.13, 0.56, 0.66, and 0.16 μM, respectively[1].
CDK7-IN-34 (0.1-3 μM; 16 h) reduces CDK1 and CDK2 phosphorylation levels and downregulates oncoprotein c-Myc expression in MDA-MB-231 cells[1].
CDK7-IN-34 (0.3-10 μM; 16 h) significantly reduces CDK1 phosphorylation and c-Myc levels in BT549 cells, but has little effect on CDK2 phosphorylation levels[1].
CDK7-IN-34 (0.1-10 μM; 48 h) significantly reduces RNA polymerase II CTD serine 7 (Ser7) phosphorylation levels in a dose-dependent manner in MDA-MB-231 and BT549 cells[1].
CDK7-IN-34 (0.1-3 μM; 16 h) reduces CDK1 and CDK2 phosphorylation levels and downregulates oncoprotein c-Myc expression in MDA-MB-231 cells[1].
CDK7-IN-34 (0.3-10 μM; 16 h) significantly reduces CDK1 phosphorylation and c-Myc levels in BT549 cells, but has little effect on CDK2 phosphorylation levels[1].
CDK7-IN-34 (0.1-10 μM; 48 h) significantly reduces RNA polymerase II CTD serine 7 (Ser7) phosphorylation levels in a dose-dependent manner in MDA-MB-231 and BT549 cells[1].
Anti-cancer
Cell Cycle Regulation
Others
CDK7-IN-34 potently inhibits CDK7/CAK with an IC50 of 3 nM, and its IC50 values against CDK2/cyclin E1 and CDK6/cyclin D3 are 3910 nM and 565.4 nM, respectively, demonstrating high selectivity[1].
CDK7-IN-34 (72 h) shows weak cytotoxicity in NCM-460, MCF-10A, and RWPE-1 normal cells, with EC50 values of 1.61, 0.94, and 2.00 μM, respectively[1].
CDK7-IN-34 (72 h) shows weak cytotoxicity in NCM-460, MCF-10A, and RWPE-1 normal cells, with EC50 values of 1.61, 0.94, and 2.00 μM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
-
Cell Line:MDA-MB-231
-
Concentration:0.1, 0.3, 1, 3 μM
-
Incubation Time:16 h (for CDKs and c-Myc) and 48 h (for RNA Pol II)
-
Result:Dose-dependently decreased the phosphorylation levels of CDK1 and CDK2, downregulated the expression level of oncoprotein c-Myc, and significantly suppressed the phosphorylation of serine 7 (Ser7) in the RNA polymerase II CTD.
Western Blot Analysis[1]
-
Cell Line:BT549
-
Concentration:0.1, 0.3, 1, 3, 10 μM
-
Incubation Time:16 h (for CDKs and c-Myc) and 48 h (for RNA Pol II)
-
Result:Dose-dependently and markedly decreased CDK1 phosphorylation and downregulated c-Myc protein expression, but had little effect on CDK2 phosphorylation; simultaneously, it significantly suppressed the phosphorylation of serine 7 (Ser7) in the RNA polymerase II CTD.
Cell Cycle Analysis[1]
-
Cell Line:MDA-MB-231
-
Concentration:0.3, 1, 3 μM
-
Incubation Time:24 h
-
Result:Induced cell cycle arrest, leading to cell accumulation at the G0/G1 phase.
Cell Cycle Analysis[1]
-
Cell Line:BT549
-
Concentration:1, 3, 10 μM
-
Incubation Time:24 h
-
Result:Induced cell cycle arrest, leading to cell accumulation at the G2/M phase.
Parmacokinetics
| Species | Dose | Route | C0 | T1/2 | AUCinf | Clearance (CL) | Vd | Cmax | Tmax | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 764 ng/mL | 4.0 h | 482 ng·h/mL | 68.9 mL/min/kg | 24.4 L/kg | / | / | / |
| Mice[1] | 6 mg/kg | p.o. | / | 1.1 h | 209 ng·h/mL | / | / | 48 ng/mL | 2.8 h | 16 % |
| Mice[1] | 20 mg/kg | p.o. | / | 3.6 h | 1088 ng·h/mL | / | / | 188 ng/mL | 3.0 h | 21 % |
| Mice[1] | 60 mg/kg | p.o. | / | 2.7 h | 4281 ng·h/mL | / | / | 569 ng/mL | 2.0 h | 28 % |
In Vivo
Anti-cancer
CDK7-IN-34 (120 h) (compound I-23) (20-40 mg/kg; p.o.; once daily; 19 days) dose-dependently inhibits tumor growth in a BALB/c nude mouse model bearing human colorectal cancer HCT116 subcutaneous xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c-nude (female, 8 weeks, 18-22 g) were subcutaneously injected with 1×106 HCT116 cells[1]
-
Dosage:20 mg/kg; 40 mg/kg
-
Administration:p.o.; once daily; 19 days
-
Result:Dose-dependently suppressed tumor growth in the HCT116 xenograft model, with tumor growth inhibition (TGI) of 33.5% at 20 mg/kg and 61.5% at 40 mg/kg.
Chemical Information
-
Molecular Weight 521.70
-
Formula C29H43N7O2
-
SMILES
CC(C1=C2N=C3N=C(N2N=C1)NCC4=CC=CC=C4OC[C@@H](CCCCC5(CN3)CCNCC5)OCC)C
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
References
Calculators
Molarity Calculator
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
=
×
×
Dilution Calculator
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CDK7-IN-34 Related Classifications
HY-191412 Related Classifications
Powered by Bioz