Details of the Drug

General Information of Drug (ID: DM9CIUW)

Drug Name

Ribociclib succinate

Synonyms

1374639-75-4; LEE011 succinate; LEE011 (succinate); UNII-BG7HLX2919; LEE011-BBA; Ribociclib succinate [USAN]; BG7HLX2919; Kisqali (TN); Ribociclib succinate (USAN); LEE-011 succinate; SCHEMBL2684999; EX-A1586; HY-15777B; 1374639-75-4 (succinate); AKOS030526460; CS-2277; ACN-040739

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Hormone receptor positive and HER2-negative advanced or metastatic breast cancer	2C60-2C65	Approved	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski):
2

Molecular Weight

552.6

Topological Polar Surface Area

Not Available

Rotatable Bond Count

8

Hydrogen Bond Donor Count

4

Hydrogen Bond Acceptor Count

11

Chemical Identifiers

Formula: C27H36N8O5
IUPAC Name: butanedioic acid;7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
Canonical SMILES: CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5.C(CC(=O)O)C(=O)O
InChI: InChI=1S/C23H30N8O.C4H6O4/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30;5-3(6)1-2-4(7)8/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28);1-2H2,(H,5,6)(H,7,8)
InChIKey: NHANOMFABJQAAH-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 57334219
CAS Number: 1374639-75-4
TTD ID: D01HVT
INTEDE ID: DR1415
ACDINA ID: D01386

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-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Breast cancer

ICD Disease Classification

2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cyclin-dependent kinase 4 (CDK4)	DTT	CDK4	3.30E-72	0.65	2.39
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	5.59E-39	-3.76E-01	-1.64E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Crospovidone	E00626	Not Available	Disintegrant
Ferric oxide black	E00522	16211978	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Magnesium stearate	E00208	11177	lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Soybean lecithin	E00637	Not Available	Other agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Xanthan gum	E00694	Not Available	Bioadhesive material; Emulsifying agent; Gelling agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
--------------------


⏷ Show the Full List of 12 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ribociclib Succinate 200mg tablet	200mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
4	P-glycoprotein limits ribociclib brain exposure and CYP3A4 restricts its oral bioavailability. Mol Pharm. 2019 Sep 3;16(9):3842-3852.
5	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
6	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
7	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
8	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
9	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
10	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
11	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
12	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
13	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
14	Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
15	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
16	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
17	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
18	Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
19	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.
20	Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
21	Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
22	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
23	Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
24	Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
25	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.