Synonym
PPDA-001; PPDA-001; PPDA-001; GTPL9903; GTPL-9903; GTPL 9903; ICEC0942; ICEC-0942; ICEC 0942; CT7001; CT-7001; CT 7001;
IUPAC/Chemical Name
(3R,4R)-4-(((7-(Benzylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)piperidin-3-ol hydrochloride
InChi Key
YMNPLAHCOLEZJE-ZFNKBKEPSA-N
InChi Code
InChI=1S/C22H30N6O.ClH/c1-15(2)18-13-26-28-21(25-11-16-6-4-3-5-7-16)10-20(27-22(18)28)24-12-17-8-9-23-14-19(17)29;/h3-7,10,13,15,17,19,23,25,29H,8-9,11-12,14H2,1-2H3,(H,24,27);1H/t17-,19+;/m1./s1
SMILES Code
O[C@H]1CNCC[C@@H]1CNC2=NC3=C(C(C)C)C=NN3C(NCC4=CC=CC=C4)=C2.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER).
In xenografts of both breast and colorectal cancers, the drug has substantial anti-tumor effects. Additionally, combination therapy with tamoxifen showed complete growth arrest of ER-positive tumor xenografts. Our findings reveal that CDK7 inhibition provides a new approach, especially for ER-positive breast cancer and identify ICEC0942 as a prototype drug with potential utility as a single agent or in combination with hormone therapies for breast cancer. ICEC0942 may also be effective in other cancers that display characteristics of transcription factor addiction, such as acute leukaemia, and small-cell lung cancer.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
430.98
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Patel H, Periyasamy M, Sava GP, Bondke A, Slafer BW, Kroll SHB, Barbazanges M,
Starkey R, Ottaviani S, Harrod A, Aboagye EO, Buluwela L, Fuchter MJ, Barrett
AGM, Coombes RC, Ali S. ICEC0942, an Orally Bioavailable Selective Inhibitor of
CDK7 for Cancer Treatment. Mol Cancer Ther. 2018 Jun;17(6):1156-1166. doi:
10.1158/1535-7163.MCT-16-0847. Epub 2018 Mar 15. PubMed PMID: 29545334.
2: Hazel P, Kroll SH, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC,
Ali S, Barrett AG, Freemont PS. Inhibitor Selectivity for Cyclin-Dependent
Kinase 7: A Structural, Thermodynamic, and Modelling Study. ChemMedChem. 2017 Mar
7;12(5):372-380. doi: 10.1002/cmdc.201600535. Epub 2017 Feb 6. Erratum in:
ChemMedChem. 2018 Jan 22;13(2):207. PubMed PMID: 28125165.
3. http://mct.aacrjournals.org/content/early/2018/03/15/1535-7163.MCT-16-0847