Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMV2DIW)

• Drug Name: BAY 10-00394 Drug Info
• Synonyms: roniciclib; BAY 1000394; BAY 10-00394; KB-145902; 1223498-69-8; Tube010; SCHEMBL875845; GTPL7874

Indication

Disease Entry	ICD 11	Status	REF
Small-cell lung cancer	2C25.Y	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 45380979
  TTD Drug ID: DMV2DIW

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 9 (CDK9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flavopiridol	DMKSUOI	Acute myeloid leukaemia	2A60	Phase 2	[4]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[5]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[8]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[4]
AZD4573	DMOYPTK	Haematological malignancy	2B33.Y	Phase 1	[4]
TP-1287	DM3Z07E	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
VIP-152	DMBQ5OL	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[10]
AZD7503	DM8XJD2	Non-alcoholic steatohepatitis	DB92.1	Phase 1	[11]

Drug(s) Targeting Cyclin-dependent kinase 1 (CDK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[5]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[5]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[13]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[16]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[17]

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[5]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[18]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[19]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[20]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]

Drug(s) Targeting Cyclin-dependent kinase 4 (CDK4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[22]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[23]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[24]
Ribociclib Succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[25]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[26]
LEE011	DMMX75K	Breast cancer	2C60-2C65	Phase 3	[27]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[5]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[3]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[4]

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 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Inhibitor	[3]
Cyclin-dependent kinase 9 (CDK9)	TT1LVF2	CDK9_HUMAN	Inhibitor	[2]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7874).
• [2] National Cancer Institute Drug Dictionary (drug id 770319).
• [3] Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [6] 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.
• [7] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [8] Clinical pipeline report, company report or official report of BioTheryX.
• [9] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [10] VIP152 is a selective CDK9 inhibitor with pre-clinical in vitro and in vivo efficacy in chronic lymphocytic leukemia. Leukemia. 2023 Feb;37(2):326-338.
• [11] ClinicalTrials.gov (NCT05560607) An Open-label, Non-randomized, Multiple-dose Study to Assess the Knockdown of Hepatic HSD17B13 mRNA Expression, Pharmacokinetics, Safety, and Tolerability Following Administration of AZD7503 in Participants With Non-alcoholic Fatty Liver Disease. U.S.National Institutes of Health.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [16] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [17] 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.
• [18] Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
• [19] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [20] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
• [21] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [22] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [23] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [26] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [27] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.