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MedKoo Cat#: 531323 | Name: PHA-767491 free base
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Description:

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

PHA 767491 hydrochloride is a potent and selective ATP-competitive dual inhibitor cdc7/cdk9. PHA-767491 blocks DNA synthesis and affects the phosphorylation of the replicative DNA helicase at Cdc7-dependent phosphorylation sites.

Chemical Structure

PHA-767491 free base
PHA-767491 free base
CAS#845714-00-3 (free base)

Theoretical Analysis

MedKoo Cat#: 531323

Name: PHA-767491 free base

CAS#: 845714-00-3 (free base)

Chemical Formula: C12H11N3O

Exact Mass: 213.0902

Molecular Weight: 213.24

Elemental Analysis: C, 67.59; H, 5.20; N, 19.71; O, 7.50

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,650.00 2 Weeks
2g USD 6,250.00 2 Weeks
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Related CAS #
942425-68-5 (HCl) 845714-00-3 (free base) 845538-12-7 (2HCl)
Synonym
PHA-767491 free base, PHA-767491; PHA 767491; PHA767491; CAY10572; CAY-10572; CAY 10572.
IUPAC/Chemical Name
1,5,6,7-Tetrahydro-2-(4-pyridinyl)-4H-pyrrolo[3,2-c]pyridin-4-one
InChi Key
DKXHSOUZPMHNIZ-UHFFFAOYSA-N
InChi Code
InChI=1S/C12H11N3O/c16-12-9-7-11(8-1-4-13-5-2-8)15-10(9)3-6-14-12/h1-2,4-5,7,15H,3,6H2,(H,14,16)
SMILES Code
O=C1C2=C(NC(C3=CC=NC=C3)=C2)CCN1
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
Soluble in DMSO
Shelf Life
>3 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
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PHA-767491 is a dual Cdc7/Cdk9 inhibitor, with IC50s of 10 nM and 34 nM, respectively.
In vitro activity:
Compared with the sole use of each agent, PHA-767491 in combination with 5-FU exhibited much stronger cytotoxicity and induced significant apoptosis manifested by remarkably increased caspase 3 activation and poly(ADP-Ribose) polymerase fragmentation in HCC cells. PHA-767491 directly counteracted the 5-FU-induced phosphorylation of Chk1, a substrate of Cdc7; and decreased the expression of the anti-apoptotic protein myeloid leukemia cell 1, a downstream target of Cdk9. In tumor tissues sectioned from nude mice HCC xenografts, administration of PHA-767491 also decreased Chk1 phosphorylation and increased in situ cell apoptosis. Reference: Curr Cancer Drug Targets. 2015;15(3):196-204. https://pubmed.ncbi.nlm.nih.gov/25643258/
In vivo activity:
PHA-767491 was originally identified as an inhibitor of CDC7/CDK9 and was found to reduce TDP-43 phosphorylation and prevent neurodegeneration in TDP-43 transgenic animals. Further study of SCA17 transgenic mice carrying human TBP-109Q showed that PHA-767491 ameliorated the gait ataxia and the inflammatory response both centrally and peripherally. Reference: J Mol Neurosci. 2020 Jul;70(7):1140-1152. https://pubmed.ncbi.nlm.nih.gov/32170713/

Preparing Stock Solutions

The following data is based on the product molecular weight 213.24 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. Erbayraktar Z, Alural B, Erbayraktar RS, Erkan EP. Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int. 2016 Nov 18;16:88. doi: 10.1186/s12935-016-0364-8. PMID: 27891063; PMCID: PMC5116134. 2. Li W, Zhao XL, Shang SQ, Shen HQ, Chen X. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204. doi: 10.2174/1568009615666150212112753. PMID: 25643258. 3. Chung YH, Lin CW, Huang HY, Chen SL, Huang HJ, Sun YC, Lee GC, Lee-Chen GJ, Chang YC, Hsieh-Li HM. Targeting Inflammation, PHA-767491 Shows a Broad Spectrum in Protein Aggregation Diseases. J Mol Neurosci. 2020 Jul;70(7):1140-1152. doi: 10.1007/s12031-020-01521-y. Epub 2020 Mar 13. PMID: 32170713.
In vitro protocol:
1. Erbayraktar Z, Alural B, Erbayraktar RS, Erkan EP. Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int. 2016 Nov 18;16:88. doi: 10.1186/s12935-016-0364-8. PMID: 27891063; PMCID: PMC5116134. 2. Li W, Zhao XL, Shang SQ, Shen HQ, Chen X. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204. doi: 10.2174/1568009615666150212112753. PMID: 25643258.
In vivo protocol:
1. Chung YH, Lin CW, Huang HY, Chen SL, Huang HJ, Sun YC, Lee GC, Lee-Chen GJ, Chang YC, Hsieh-Li HM. Targeting Inflammation, PHA-767491 Shows a Broad Spectrum in Protein Aggregation Diseases. J Mol Neurosci. 2020 Jul;70(7):1140-1152. doi: 10.1007/s12031-020-01521-y. Epub 2020 Mar 13. PMID: 32170713.
 1: Li W, Zhao XL, Shang SQ, Shen HQ, Chen X. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204. PubMed PMID: 25643258. 2: Sasi NK, Tiwari K, Soon FF, Bonte D, Wang T, Melcher K, Xu HE, Weinreich M. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. PLoS One. 2014 Nov 20;9(11):e113300. doi: 10.1371/journal.pone.0113300. eCollection 2014. PubMed PMID: 25412417; PubMed Central PMCID: PMC4239038. 3: Poh WT, Chadha GS, Gillespie PJ, Kaldis P, Blow JJ. Xenopus Cdc7 executes its essential function early in S phase and is counteracted by checkpoint-regulated protein phosphatase 1. Open Biol. 2014 Jan 8;4:130138. doi: 10.1098/rsob.130138. PubMed PMID: 24403013; PubMed Central PMCID: PMC3909274. 4: Natoni A, Coyne MR, Jacobsen A, Rainey MD, O'Brien G, Healy S, Montagnoli A, Moll J, O'Dwyer M, Santocanale C. Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models. Cancers (Basel). 2013 Jul 24;5(3):901-18. doi: 10.3390/cancers5030901. PubMed PMID: 24202326; PubMed Central PMCID: PMC3795371. 5: Rainey MD, Harhen B, Wang GN, Murphy PV, Santocanale C. Cdc7-dependent and -independent phosphorylation of Claspin in the induction of the DNA replication checkpoint. Cell Cycle. 2013 May 15;12(10):1560-8. doi: 10.4161/cc.24675. Epub 2013 Apr 17. PubMed PMID: 23598722; PubMed Central PMCID: PMC3680535. 6: Liachko NF, McMillan PJ, Guthrie CR, Bird TD, Leverenz JB, Kraemer BC. CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Ann Neurol. 2013 Jul;74(1):39-52. doi: 10.1002/ana.23870. Epub 2013 Jul 8. PubMed PMID: 23424178; PubMed Central PMCID: PMC3775949. 7: Natoni A, Murillo LS, Kliszczak AE, Catherwood MA, Montagnoli A, Samali A, O'Dwyer M, Santocanale C. Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells. Mol Cancer Ther. 2011 Sep;10(9):1624-34. doi: 10.1158/1535-7163.MCT-10-1119. Epub 2011 Jul 18. PubMed PMID: 21768328. 8: Yecies D, Carlson NE, Deng J, Letai A. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 2010 Apr 22;115(16):3304-13. doi: 10.1182/blood-2009-07-233304. Epub 2010 Mar 2. PubMed PMID: 20197552; PubMed Central PMCID: PMC2858493. 9: Jackson PK. Stopping replication, at the beginning. Nat Chem Biol. 2008 Jun;4(6):331-2. doi: 10.1038/nchembio0608-331. PubMed PMID: 18488006. 10: Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008 Jun;4(6):357-65. doi: 10.1038/nchembio.90. Epub 2008 May 11. PubMed PMID: 18469809.