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

General Information of Drug (ID: DMI7AUJ)

• Drug Name: PYRAZOLOPYRIDAZINE 2 Drug Info
• Synonyms: PYRAZOLOPYRIDAZINE 2; pyrazolo[1,5-b]pyridazine deriv. 25; AC1O6ZJ2; BDBM8134; CHEMBL186054; N-(3,4-dimethoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine

Indication

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

• Cross-matching ID:
  PubChem CID: 6539367
  TTD Drug ID: DMI7AUJ

Molecule-Related Drug Atlas

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	[2]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[4]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[5]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[10]

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	[11]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[12]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[13]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[14]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[15]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[16]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[17]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[18]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[19]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[20]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[21]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[22]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[23]
Ribociclib succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[24]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[25]
LEE011	DMMX75K	Breast cancer	2C60-2C65	Phase 3	[26]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[2]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[27]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[10]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Inhibitor	[1]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]

References

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• [2] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [3] 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.
• [4] 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.
• [5] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [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] 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.
• [8] 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.
• [9] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [13] 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.
• [14] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [15] 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.
• [16] Company report (Neurim Pharmaceuticals)
• [17] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [18] 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.
• [19] 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.
• [20] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [21] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [22] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [26] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
• [27] Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.