PHA-793887 | CAS#718630-59-2 | CAS#718630-60-5 | CDK inhibitor

MedKoo Cat#: 206024 | Name: PHA-793887

Description:

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

PHA-793887 is an inhibitor of multiple cyclin dependent kinases (CDK) with activity against CDK2, CDK1 and CDK4. PHA-793887 was cytotoxic for leukemic cell lines in vitro, with IC(50) ranging from 0.3 to 7 microM. In colony assays PHA-793887 showed very high activity against leukemia cell lines, with an IC(50) <0.1 microM indicating that it has efficient and prolonged antiproliferative activity. PHA-793887 induced cell-cycle arrest, inhibited Rb and nucleophosmin phosphorylation. PHA-793887 has promising therapeutic activity against acute leukemias in vitro and in vivo.

Chemical Structure

PHA-793887

CAS#718630-59-2 (free base)

Theoretical Analysis

MedKoo Cat#: 206024

Name: PHA-793887

CAS#: 718630-59-2 (free base)

Chemical Formula: C19H31N5O2

Exact Mass: 361.2478

Molecular Weight: 361.48

Elemental Analysis: C, 63.13; H, 8.64; N, 19.37; O, 8.85

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	2 Weeks

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Related CAS #

718630-60-5 (HCl) 718630-59-2 (free base)

Synonym

PHA793887; PHA 793887; PHA-793887.

IUPAC/Chemical Name

N-(6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-3-methylbutanamide

InChi Key

HUXYBQXJVXOMKX-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H31N5O2/c1-12(2)10-15(25)20-17-14-11-24(19(3,4)16(14)21-22-17)18(26)13-6-8-23(5)9-7-13/h12-13H,6-11H2,1-5H3,(H2,20,21,22,25)

SMILES Code

CC(C)CC(NC1=NNC2=C1CN(C(C3CCN(C)CC3)=O)C2(C)C)=O

Appearance

White 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, not soluble in water.

Shelf Life

>5 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

Related CAS# 718630-59-2 (free base) 718630-60-5 ( HCl salt)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC61102

View CoA: current batch, Lot#BBC61118

QC Data

View QC data: current batch, Lot#BBC61102

View QC data: current batch, Lot#BBC61118

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PHA-793887 is an ATP-competitive CDK inhibitor, can inhibit Cdk2, Cdk1, Cdk4, and Cdk9 with IC50s of 8 nM, 60 nM, 62 nM and 138 nM, respectively, and also inhibits glycogen synthase kinase 3β with an IC50 of 79 nM.

In vitro activity:

Subsequently, this study examined the effects of PHA-793887 on osteosarcoma cells in vitro. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the viability of MG63, U20S and 143B cells decreased with increasing drug concentrations (P < 0.05; Figure 5A). Moreover, in a colony formation assay, the PHA-793887-treated cells exhibited lower clonogenicity than the control cells in both number and size (Figure 5B, 5D). Reference: Aging (Albany NY). 2021 Jun 21;13. https://www.aging-us.com/article/203165/text

In vivo activity:

On the basis of these data compound 31 (PHA-793887) was evaluated for its in vivo antitumor activity in the human ovarian A2780 xenograft mouse model. The doses of 10, 20 and 30 mg/kg were selected and administered by iv route, once a day, for 10 consecutive days, on the basis of the plasma levels reached in the preliminary in vivo PK study. Compound 31 was dissolved in 5% dextrose solution and caused a dose-dependent inhibition of the A2780 tumor growth up to 76% at the dose of 30 mg/kg at the end of treatment (Fig. 4a). With the same schedule, compound 31 was tested at the doses of 10 and 20 mg/kg also on a model of human colon carcinoma (HCT-116) causing a dose-dependent inhibition of the tumor growth up to 81% at the dose of 20 mg/kg at the end of treatment (Fig. 4b) and on a model of human pancreatic carcinoma (BX-PC3) with a 84% of tumor growth inhibition at the end of treatment with 20 mg/kg (Fig. 4c). Compound 31 was well tolerated upon daily treatments by iv administration. In fact, in all experiments, body weight reduction was always marginal (<10% vs control mice) and no toxic effects were reported after gross autopsy. Reference: Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. https://pubmed.ncbi.nlm.nih.gov/20153204/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	83.00
	Ethanol	30.0	83.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 361.48 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

Formulation protocol:

1. Wu B, Yang W, Fu Z, Xie H, Guo Z, Liu D, Ge J, Zhong S, Liu L, Liu J, Zhu D. Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma. Aging (Albany NY). 2021 Jun 21;13. doi: 10.18632/aging.203165. Epub ahead of print. PMID: 34156352. 2. Alzani R, Pedrini O, Albanese C, Ceruti R, Casolaro A, Patton V, Colotta F, Rambaldi A, Introna M, Pesenti E, Ciomei M, Golay J. Therapeutic efficacy of the pan-cdk inhibitor PHA-793887 in vitro and in vivo in engraftment and high-burden leukemia models. Exp Hematol. 2010 Apr;38(4):259-269.e2. doi: 10.1016/j.exphem.2010.02.004. Epub 2010 Feb 16. PMID: 20167248. 3. Brasca MG, Albanese C, Alzani R, Amici R, Avanzi N, Ballinari D, Bischoff J, Borghi D, Casale E, Croci V, Fiorentini F, Isacchi A, Mercurio C, Nesi M, Orsini P, Pastori W, Pesenti E, Pevarello P, Roussel P, Varasi M, Volpi D, Vulpetti A, Ciomei M. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. doi: 10.1016/j.bmc.2010.01.042. Epub 2010 Jan 25. PMID: 20153204.

In vitro protocol:

In vivo protocol:

1. Alzani R, Pedrini O, Albanese C, Ceruti R, Casolaro A, Patton V, Colotta F, Rambaldi A, Introna M, Pesenti E, Ciomei M, Golay J. Therapeutic efficacy of the pan-cdk inhibitor PHA-793887 in vitro and in vivo in engraftment and high-burden leukemia models. Exp Hematol. 2010 Apr;38(4):259-269.e2. doi: 10.1016/j.exphem.2010.02.004. Epub 2010 Feb 16. PMID: 20167248. 2. Brasca MG, Albanese C, Alzani R, Amici R, Avanzi N, Ballinari D, Bischoff J, Borghi D, Casale E, Croci V, Fiorentini F, Isacchi A, Mercurio C, Nesi M, Orsini P, Pastori W, Pesenti E, Pevarello P, Roussel P, Varasi M, Volpi D, Vulpetti A, Ciomei M. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. doi: 10.1016/j.bmc.2010.01.042. Epub 2010 Jan 25. PMID: 20153204.

1: Massard C, Soria JC, Anthoney DA, Proctor A, Scaburri A, Pacciarini MA, Laffranchi B, Pellizzoni C, Kroemer G, Armand JP, Balheda R, Twelves CJ. A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle. 2011 Mar 15;10(6):963-70. Epub 2011 Mar 15. PubMed PMID: 21368575. 2: Zoubir M, Flament C, Gdoura A, Bahleda R, Litvinova E, Soumelis V, Conforti R, Viaud S, Soria JC, Kroemer G, Zitvogel L, Chaput N. An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases the susceptibility of cancer patients to herpesviridae. Cell Cycle. 2011 Jan 1;10(1):118-26. Epub 2011 Jan 1. PubMed PMID: 21200142. 3: Iorio F, Bosotti R, Scacheri E, Belcastro V, Mithbaokar P, Ferriero R, Murino L, Tagliaferri R, Brunetti-Pierri N, Isacchi A, di Bernardo D. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6. doi: 10.1073/pnas.1000138107. Epub 2010 Aug 2. PubMed PMID: 20679242; PubMed Central PMCID: PMC2930479. 4: Locatelli G, Bosotti R, Ciomei M, Brasca MG, Calogero R, Mercurio C, Fiorentini F, Bertolotti M, Scacheri E, Scaburri A, Galvani A, Pesenti E, De Baere T, Soria JC, Lazar V, Isacchi A. Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study. Mol Cancer Ther. 2010 May;9(5):1265-73. doi: 10.1158/1535-7163.MCT-09-1163. Epub 2010 Apr 27. PubMed PMID: 20423997. 5: Alzani R, Pedrini O, Albanese C, Ceruti R, Casolaro A, Patton V, Colotta F, Rambaldi A, Introna M, Pesenti E, Ciomei M, Golay J. Therapeutic efficacy of the pan-cdk inhibitor PHA-793887 in vitro and in vivo in engraftment and high-burden leukemia models. Exp Hematol. 2010 Apr;38(4):259-269.e2. doi: 10.1016/j.exphem.2010.02.004. Epub 2010 Feb 16. PubMed PMID: 20167248. 6: Brasca MG, Albanese C, Alzani R, Amici R, Avanzi N, Ballinari D, Bischoff J, Borghi D, Casale E, Croci V, Fiorentini F, Isacchi A, Mercurio C, Nesi M, Orsini P, Pastori W, Pesenti E, Pevarello P, Roussel P, Varasi M, Volpi D, Vulpetti A, Ciomei M. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. doi: 10.1016/j.bmc.2010.01.042. Epub 2010 Jan 25. PubMed PMID: 20153204.