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

General Information of Drug (ID: DMP08BY)

• Drug Name: RGB-286147 Drug Info
• Synonyms: pyrazolopyrimidone analog, RGB-286147

Indication

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

• Cross-matching ID:
  PubChem CID: 135473382
  CAS Number: CAS 784211-09-2
  TTD Drug ID: DMP08BY

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 7 (CDK7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[3]
Samuraciclib	DM54FQA	Breast cancer	2C60-2C65	Phase 1/2	[4]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[6]
SY-1365	DMK48PM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
LY3405105	DMB51K2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
SY-5609	DMNW3LH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[10]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[10]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[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	Bipolar disorder	6A60	Phase 2	[13]
Tideglusib	DME4LA1	Alzheimer disease	8A20	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 6 (CDK6)

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]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[7]
GLR2007	DM7DWLY	Glioblastoma of brain	2A00.00	Phase 1/2	[27]
FCN-437	DMQ8VUW	Breast cancer	2C60-2C65	Phase 1/2	[28]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 7 (CDK7)	TTQYF7G	CDK7_HUMAN	Inhibitor	[2]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_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: 5943).
• [2] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [3] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [4] The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer. Br J Cancer. 2023 Jun;128(12):2326-2337.
• [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 the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823.
• [9] Clinical pipeline report, company report or official report of Syros Pharmaceuticals.
• [10] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [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] Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
• [28] Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
• [29] 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.