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

General Information of Drug (ID: DMMX75K)

• Drug Name: LEE011 Drug Info
• Synonyms: Ribociclib; LEE011; 1211441-98-3; LEE-011; Kisqali; Ribociclib(LEE011); UNII-TK8ERE8P56; LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; TK8ERE8P56; Ribociclib (LEE011); AK174906; 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo [2,3-d]pyrimidine-6-carboxylic acid dimethylamide; Ribociclib [USAN:INN]; LEE011A; Tube013

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 44631912
  CAS Number: CAS 1211441-98-3
  TTD Drug ID: DMMX75K

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[5]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[6]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[7]
Ribociclib Succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[8]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[9]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[11]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[12]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[1]
GLR2007	DM7DWLY	Glioblastoma of brain	2A00.00	Phase 1/2	[13]

Drug(s) Targeting Cyclin-dependent kinase 6 (CDK6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[5]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[6]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[7]
Ribociclib Succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[8]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[9]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[1]
GLR2007	DM7DWLY	Glioblastoma of brain	2A00.00	Phase 1/2	[13]
FCN-437	DMQ8VUW	Breast cancer	2C60-2C65	Phase 1/2	[14]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[15]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]

Drug(s) Affected By Alanine aminotransferase 1 (GPT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Halothane	DM80OZ5	Anaesthesia	9A78.6	Approved	[17]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[17]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[17]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[17]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[4]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[20]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[4]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Modulator	[3]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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: 7383).
• [3] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
• [4] Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
• [5] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [10] 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.
• [11] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [12] Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
• [13] Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
• [14] Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
• [15] 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.
• [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] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [18] Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. doi: 10.1002/jbt.22369. Epub 2019 Jul 23.
• [19] Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1/GSTA1 expression via JNK signaling pathway. J Appl Toxicol. 2021 Dec;41(12):2011-2020. doi: 10.1002/jat.4181. Epub 2021 May 6.
• [20] A Study of Gentianae Radix et Rhizoma Class Differences Based on Chemical Composition and Core Efficacy. Molecules. 2023 Oct 17;28(20):7132. doi: 10.3390/molecules28207132.