PHA-793887
featured

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

MedKoo CAT#: 206024

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

Description: 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

img
PHA-793887
CAS# 718630-59-2 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206024
Name: PHA-793887
CAS#: 718630-59-2 (free base)
Chemical Formula: C19H31N5O2
Exact Mass: 361.25
Molecular Weight: 361.480
Elemental Analysis: C, 63.13; H, 8.64; N, 19.37; O, 8.85

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 850 Ready to ship
500mg USD 1950 Ready to ship
1g USD 2950 2 Weeks
Bulk inquiry

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)      

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 30.0 83.00
Ethanol 30.0 83.00

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.

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. 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: 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.
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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.