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

General Information of Drug (ID: DMB9F2L)

• Drug Name: PMID19115845C89S Drug Info
• Synonyms: 3du8; GTPL8114; BDBM27380; DB07149

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 16757525
  TTD Drug ID: DMB9F2L

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	[2]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[3]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[4]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[6]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[2]
AZD4573	DMOYPTK	Haematological malignancy	2B33.Y	Phase 1	[2]
TP-1287	DM3Z07E	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[8]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[8]

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	[3]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[3]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[10]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[4]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[8]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[12]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[13]

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	[3]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[14]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[15]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[4]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[2]

Drug(s) Targeting Glycogen synthase kinase-3 beta (GSK-3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMO-02	DMJRU3A	Myotonic dystrophy	8C71.0	Phase 2/3	[17]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[18]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[19]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[20]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[21]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[22]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[23]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[24]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[25]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[26]

Drug(s) Targeting CDC7-related kinase (CDC7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-863233	DM5HUY8	Haematological malignancy	2B33.Y	Phase 1/2	[27]
TAK-931	DM1ALY9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
PMID26161698-Compound-44	DM8UPO3	N. A.	N. A.	Patented	[8]
PMID20873740C18	DMVHR3Z	Discovery agent	N.A.	Investigative	[28]
PMID24793884C74	DMFSJQC	Discovery agent	N.A.	Investigative	[29]
PMID24793884C77	DMZENGX	Discovery agent	N.A.	Investigative	[29]
PHA-767491	DM4H7D5	Discovery agent	N.A.	Investigative	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CDC7-related kinase (CDC7)	TTSMTDI	CDC7_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 9 (CDK9)	TT1LVF2	CDK9_HUMAN	Inhibitor	[1]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]
TAO kinase 3 (TAOK3)	TTO7L0V	TAOK3_HUMAN	Inhibitor	[1]

References

• [1] First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem. 2009 Jan 22;52(2):293-307.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [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] 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.
• [15] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [16] 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.
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [19] The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
• [20] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [21] 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
• [22] Company report (Neurim Pharmaceuticals)
• [23] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [24] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [25] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
• [26] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [27] Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.
• [28] Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding. J Med Chem. 2010 Oct 28;53(20):7296-315.
• [29] Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors. Eur J Med Chem. 2014 Jun 10;80:364-82.
• [30] Drug design with Cdc7 kinase: a potential novel cancer therapy target. Drug Des Devel Ther. 2009 Feb 6;2:255-64.