Details of the Drug

General Information of Drug (ID: DM9DJL2)

• Drug Name: P276-00
• Synonyms: CHEMBL2312181; SCHEMBL1180418

Indication

Disease Entry	ICD 11	Status	REF
Mantle cell lymphoma	2A85.5	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 438.3
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 3
  Hydrogen Bond Donor Count; 4
  Hydrogen Bond Acceptor Count; 6
• Chemical Identifiers:
  Formula: C21H21Cl2NO5
  IUPAC Name: 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one;hydrochloride
  Canonical SMILES: CN1CC[C@H]([C@@H]1CO)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O.Cl
  InChI: InChI=1S/C21H20ClNO5.ClH/c1-23-7-6-12(14(23)10-24)19-15(25)8-16(26)20-17(27)9-18(28-21(19)20)11-4-2-3-5-13(11)22;/h2-5,8-9,12,14,24-26H,6-7,10H2,1H3;1H/t12-,14+;/m1./s1
  InChIKey: OOVTUOCTLAERQD-OJMBIDBESA-N
• Cross-matching ID:
  PubChem CID: 23643975
  CAS Number: 920113-03-7
  TTD ID: D05IRT

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 9 (CDK9)	TT1LVF2	CDK9_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Mantle cell lymphoma
• ICD Disease Classification: 2A85.5

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cyclin-dependent kinase 1 (CDK1)	DTT	CDK1	5.27E-108	1.97	3.12
Cyclin-dependent kinase 9 (CDK9)	DTT	CDK9	4.38E-01	-0.04	-0.1
Cyclin-dependent kinase 4 (CDK4)	DTT	CDK4	3.30E-72	0.65	2.39

References

• [1] A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2015 Jul;15(7):392-7.
• [2] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
• [5] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [6] Clinical pipeline report, company report or official report of BioTheryX.
• [7] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [8] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [9] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [10] P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
• [11] 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 h... Cell Cycle. 2011 Mar 15;10(6):963-70.
• [12] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [13] Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
• [14] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [15] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [19] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
• [20] Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
• [21] Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.