MedKoo Cat#: 407248 | Name: Senexin B
Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Senexin B is a potent and selective CDK8/19 inhibitor. Senexin B inhibits CDK8/19 in low nanomolar range in vitro and in vivo as an ATP pocket binder, with very high target selectivity as indicated by kinome profiling. It is highly water-soluble, bioavailable, and produces no limiting toxicity upon prolonged administration in mice, at doses that yield plasma concentrations exceeding cellular IC50 by 2-3 orders of magnitude. CDK8/19 inhibition produces chemopotentiating, chemopreventive and anti-metastatic effects in different types of cancer, inhibiting tumor progression by acting both at the tumor cells (the “seed”) and the tumor microenvironment (the “soil”) of cancers.

Chemical Structure

Senexin B
CAS#1449228-40-3

Theoretical Analysis

MedKoo Cat#: 407248

Name: Senexin B

CAS#: 1449228-40-3

Chemical Formula: C27H26N6O

Exact Mass: 450.2168

Molecular Weight: 450.55

Elemental Analysis: C, 71.98; H, 5.82; N, 18.65; O, 3.55

Price and Availability

Size Price Availability Quantity
5mg USD 325.00 2 Weeks
10mg USD 550.00 2 Weeks
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
Senexin B
IUPAC/Chemical Name
4-((2-(6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl)ethyl)amino)quinazoline-6-carbonitrile
InChi Key
VNADJTWHOAMTLY-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H26N6O/c1-32-10-12-33(13-11-32)27(34)23-6-5-21-14-19(2-4-22(21)16-23)8-9-29-26-24-15-20(17-28)3-7-25(24)30-18-31-26/h2-7,14-16,18H,8-13H2,1H3,(H,29,30,31)
SMILES Code
O=C(C1=CC2=CC=C(CCNC3=C4C(C=CC(C#N)=C4)=NC=N3)C=C2C=C1)N5CCN(C)CC5
Appearance
Solid powder
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
To be determined
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
Abstract PR08: Targeting tumor microenvironment with selective small-molecule inhibitors of CDK8/19. Donald C. Porter1, Mengqian Chen2, Jiaxin Liang2, Vimala Kaza1, Alexander Chumanevich1, Serena Altilia1, Elena Farmaki3, Marj Pena2, Gary P. Schools2, Ioulia Chatzistamou3, Lawrence T. Friedhoff1, Mark P. Wentland4, Eugenia V. Broude2, Hippokratis Kiaris3, and Igor B. Roninson2. Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; February 26 — March 1, 2014; San Diego, CA
Product Data
Certificate of Analysis
Safety Data Sheet (SDS)
Biological target:
Senexin B inhibits Cdk8 with IC50 values ranging from 24 to 50 nM, depending on the assay used. It selectively inhibits Cdk19 and Cdk8 by 98.6 and 97.8%, respectively, in a panel of greater than 450 kinases at 2 μM but does inhibit MAP4K2 and YSK4 by 69 and 59%, respectively.
In vitro activity:
Senexin B increased colon adenocarcinoma cell line HCT116 cell sensitivity to radiotherapy by mechanisms dependent and independent of p53 status. The effect of senexin B in cells with intact p53 is similar to that of Tp53 gene knockout: irradiated HCT116p53KO cells passed through the interphase and died independently of senexin B. Senexin B reduced the ability of cells to colony formation in response to irradiation. Reference: Bull Exp Biol Med. 2023 Mar;174(5):659-665. https://pubmed.ncbi.nlm.nih.gov/37060380/
In vivo activity:
CDK8 inhibitors, such as senexin B, have potential in for estrogen receptor-positive breast cancer therapy. Treatment with senexin B suppressed tumor growth and augmented the effects of fulvestrant in estrogen receptor-positive breast cancer xenografts. Reference: Oncotarget. 2017 Feb 21;8(8):12558-12575. https://pubmed.ncbi.nlm.nih.gov/28147342/

Preparing Stock Solutions

The following data is based on the product molecular weight 450.55 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.

Recalculate based on batch purity %
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
Formulation protocol:
1. Kokinos EK, Tsymbal SA, Galochkina AV, Bezlepkina SA, Nikolaeva JV, Vershinina SO, Shtro AA, Tatarskiy VV, Shtil AA, Broude EV, Roninson IB, Dukhinova M. Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes. Viruses. 2023 May 31;15(6):1292. doi: 10.3390/v15061292. PMID: 37376593; PMCID: PMC10305654. 2. Kuchur OA, Zavisrskiy AV, Shtil AA. Transcriptional Reprogramming Regulates Tumor Cell Survival in Response to Ionizing Radiation: a Role of p53. Bull Exp Biol Med. 2023 Mar;174(5):659-665. doi: 10.1007/s10517-023-05764-8. Epub 2023 Apr 15. PMID: 37060380. 3. McDermott MS, Chumanevich AA, Lim CU, Liang J, Chen M, Altilia S, Oliver D, Rae JM, Shtutman M, Kiaris H, Győrffy B, Roninson IB, Broude EV. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017 Feb 21;8(8):12558-12575. doi: 10.18632/oncotarget.14894. PMID: 28147342; PMCID: PMC5355036.
In vitro protocol:
1. Kokinos EK, Tsymbal SA, Galochkina AV, Bezlepkina SA, Nikolaeva JV, Vershinina SO, Shtro AA, Tatarskiy VV, Shtil AA, Broude EV, Roninson IB, Dukhinova M. Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes. Viruses. 2023 May 31;15(6):1292. doi: 10.3390/v15061292. PMID: 37376593; PMCID: PMC10305654. 2. Kuchur OA, Zavisrskiy AV, Shtil AA. Transcriptional Reprogramming Regulates Tumor Cell Survival in Response to Ionizing Radiation: a Role of p53. Bull Exp Biol Med. 2023 Mar;174(5):659-665. doi: 10.1007/s10517-023-05764-8. Epub 2023 Apr 15. PMID: 37060380.
In vivo protocol:
1. McDermott MS, Chumanevich AA, Lim CU, Liang J, Chen M, Altilia S, Oliver D, Rae JM, Shtutman M, Kiaris H, Győrffy B, Roninson IB, Broude EV. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017 Feb 21;8(8):12558-12575. doi: 10.18632/oncotarget.14894. PMID: 28147342; PMCID: PMC5355036.
1: Kokinos EK, Tsymbal SA, Galochkina AV, Bezlepkina SA, Nikolaeva JV, Vershinina SO, Shtro AA, Tatarskiy VV, Shtil AA, Broude EV, Roninson IB, Dukhinova M. Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes. Viruses. 2023 May 31;15(6):1292. doi: 10.3390/v15061292. PMID: 37376593; PMCID: PMC10305654. 2: Kuchur OA, Zavisrskiy AV, Shtil AA. Transcriptional Reprogramming Regulates Tumor Cell Survival in Response to Ionizing Radiation: a Role of p53. Bull Exp Biol Med. 2023 Mar;174(5):659-665. doi: 10.1007/s10517-023-05764-8. Epub 2023 Apr 15. PMID: 37060380. 3: Sakuma K, Tsubooka-Yamazoe N, Hashimoto K, Sakai N, Asano S, Watanabe- Matsumoto S, Watanabe T, Saito B, Matsumoto H, Ueno H, Ito R, Toyoda T. CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs. Stem Cell Res Ther. 2023 Jan 5;14(1):1. doi: 10.1186/s13287-022-03220-4. PMID: 36600289; PMCID: PMC9814340. 4: Ding X, Sharko AC, McDermott MSJ, Schools GP, Chumanevich A, Ji H, Li J, Zhang L, Mack ZT, Sikirzhytski V, Shtutman M, Ivers L, O'Donovan N, Crown J, Győrffy B, Chen M, Roninson IB, Broude EV. Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2201073119. doi: 10.1073/pnas.2201073119. Epub 2022 Aug 1. PMID: 35914167; PMCID: PMC9371674. 5: Zhang L, Cheng C, Li J, Wang L, Chumanevich AA, Porter DC, Mindich A, Gorbunova S, Roninson IB, Chen M, McInnes C. A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor- Enriched Pharmacokinetics. J Med Chem. 2022 Feb 24;65(4):3420-3433. doi: 10.1021/acs.jmedchem.1c01951. Epub 2022 Feb 3. PMID: 35114084; PMCID: PMC10042267. 6: Chen M, Li J, Liang J, Thompson ZS, Kathrein K, Broude EV, Roninson IB. Systemic Toxicity Reported for CDK8/19 Inhibitors CCT251921 and MSC2530818 Is Not Due to Target Inhibition. Cells. 2019 Nov 9;8(11):1413. doi: 10.3390/cells8111413. PMID: 31717492; PMCID: PMC6912361. 7: McDermott MS, Chumanevich AA, Lim CU, Liang J, Chen M, Altilia S, Oliver D, Rae JM, Shtutman M, Kiaris H, Győrffy B, Roninson IB, Broude EV. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017 Feb 21;8(8):12558-12575. doi: 10.18632/oncotarget.14894. PMID: 28147342; PMCID: PMC5355036.