Cofttek holdings limited

CDK&Aurora kinase

Dinaciclib (SCH727965) (779353-01-4)

Dinaciclib (SCH727965) is a novel and potent CDK inhibitor for CDK2, CDK5, CDK1 and CDK9 with IC50 of 1 nM, 1 nM, 3 nM and 4 nM, respectively. It also blocks thymidine (dThd) DNA incorporation. Phase 3.

Not Intended for Therapeutic Use. For research use only.

CAS: 779353-01-4 Category

Dinaciclib (SCH727965) (779353-01-4) Description

Dinaciclib, also known as SCH727965, is a potent CDK inhibitor with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9 activity in vitro with IC(50) values of 1, 1, 3, and 4 nmol/L, respectively. Compared with flavopiridol, Dinaciclib exhibits superior activity with an improved therapeutic index. Dinaciclib induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level.

In vitro cell growth of pancreatic cancer cells is inhibited by Dinaciclib (SCH727965) in a dose-dependent manner. Upon incubation with Dinaciclib for 72 h, the GI50s are approximately 10 and 20 nM for MIAPaCa-2 and Pa20C cells, respectively. These results are consistent with studies of Dinaciclib in other cancer cell lines. In soft agar assays, 5 to 10 nM of Dinaciclib significantly reduces colony formation and anchorage independent growth of MIAPaCa-2 cells. Moreover, in vitro cell migration of Pa20C and MIAPaCa-2 cells is significantly reduced by Dinaciclib-concentrations starting from 2-5 nM, as demonstrated using BD FluoroChrom, modified Boyden Chamber and wound healing assays.

 

Dinaciclib (SCH727965) (779353-01-4) Specifications

Product Name Dinaciclib (SCH727965)
Synonyms SCH 727965; SCH727965; SCH-727965; PS095760; PS 095760; PS-095760; Dinaciclib.
Chemical Names (S)-3-(((3-ethyl-5-(2-(2-hydroxyethyl)piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)pyridine 1-oxide
Purity ≥98% (HPLC)
CAS Number 779353-01-4
Molecular Formula C21H28N6O2
Molecular Weight 396.48602
Monoisotopic Mass 396.22737 g/mol
MDL number MFCD16037702
InChIKey PIMQWRZWLQKKBJ-SFHVURJKSA-N
InChi Code InChI=1S/C21H28N6O2/c1-2-17-14-23-27-19(22-13-16-6-5-9-25(29)15-16)12-20(24-21(17)27)26-10-4-3-7-18(26)8-11-28/h5-6,9,12,14-15,18,22,28H,2-4,7-8,10-11,13H2,1H3/t18-/m0/s1
SMILES CC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCCC4CCO
Form Powder
Color Light brown solid
Solubility  DMSO (>20 mg/ml)
Storage Temp.  −20°C
Shelf life >2 years if stored properly.
Handling Protect from air and light
Application A novel and potent CDK inhibitor

 


=

RIDADR NONH for all modes of transport

References:

  • Nemunaitis JJ, Small KA, Kirschmeier P, Zhang D, Zhu Y, Jou YM, Statkevich P, Yao SL, Bannerji R. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies. J Transl Med. 2013 Oct 16;11(1):259. [Epub ahead of print] PubMed PMID: 24131779; PubMed Central PMCID: PMC3853718.
  • Martin MP, Olesen SH, Georg GI, Schönbrunn E. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol. 2013 Nov 15;8(11):2360-5. doi: 10.1021/cb4003283. Epub 2013 Sep 10. PubMed PMID: 24007471; PubMed Central PMCID: PMC3846258.
  • Gojo I, Sadowska M, Walker A, Feldman EJ, Iyer SP, Baer MR, Sausville EA, Lapidus RG, Zhang D, Zhu Y, Jou YM, Poon J, Small K, Bannerji R. Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias. Cancer Chemother Pharmacol. 2013 Oct;72(4):897-908. doi: 10.1007/s00280-013-2249-z. Epub 2013 Aug 15. PubMed PMID: 23949430; PubMed Central PMCID: PMC3784060.
  • Desai BM, Villanueva J, Nguyen TT, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KS, Herlyn M. The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One. 2013;8(3):e59588. doi: 10.1371/journal.pone.0059588. Epub 2013 Mar 18. PubMed PMID: 23527225; PubMed Central PMCID: PMC3601112.
  • Zhang D, Mita M, Shapiro GI, Poon J, Small K, Tzontcheva A, Kantesaria B, Zhu Y, Bannerji R, Statkevich P. Effect of aprepitant on the pharmacokinetics of the cyclin-dependent kinase inhibitor dinaciclib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2012 Dec;70(6):891-8. doi: 10.1007/s00280-012-1967-y. Epub 2012 Oct 9. PubMed PMID: 23053255.