Details of the Drug Combination

General Information of Drug Combination (ID: DC55CN2)

• Drug Combination Name: Dianicline + SR141716A
• Indication: Tobacco dependence; Status: Discontinued [1]
• Component Drugs:
  Dianicline (DMX2SHT): Small molecular drug
  SR141716A (DMCO5JZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dianicline

Disease Entry	ICD 11	Status	REF
Tobacco dependence	6C4A.2	Discontinued in Phase 3	[2]

Dianicline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Neuronal acetylcholine receptor alpha-4/beta-2 (CHRNA4/B2)	TTL1ATN	ACHA4_HUMAN; ACHB2_HUMAN	Modulator	[4]

Indication(s) of SR141716A

Disease Entry	ICD 11	Status	REF
Obesity	5B81	Approved	[3]

SR141716A Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cannabinoid receptor 1 (CB1)	TT6OEDT	CNR1_HUMAN	Antagonist	[6]

SR141716A Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Decreases Phosphorylation	[7]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Expression	[7]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Increases Expression	[7]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Decreases Expression	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[9]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Affects Localization	[9]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Affects Localization	[9]
Hepatocyte nuclear factor 4-alpha (HNF4A)	OTY1TOAB	HNF4A_HUMAN	Decreases Activity	[10]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[9]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[11]
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Decreases Expression	[7]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027143)
• [2] Emerging drugs for the treatment of tobacco dependence. Expert Opin Emerg Drugs. 2009 Mar;14(1):23-32.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Dianicline, a novel 42 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.Nicotine Tob Res.2011 Jan;13(1):1-6.
• [5] Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2011 Apr 28;2(4):e152. doi: 10.1038/cddis.2011.36.
• [6] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [7] Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions in the mouse colon. Int J Cancer. 2009 Sep 1;125(5):996-1003. doi: 10.1002/ijc.24483.
• [8] Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss. BMC Endocr Disord. 2017 Jul 14;17(1):41. doi: 10.1186/s12902-017-0194-2.
• [9] The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. Mol Pharmacol. 2006 Oct;70(4):1298-306. doi: 10.1124/mol.106.025601. Epub 2006 Jul 5.
• [10] Rimonabant suppresses RNA transcription of hepatitis B virus by inhibiting hepatocyte nuclear factor 4. Microbiol Immunol. 2020 May;64(5):345-355. doi: 10.1111/1348-0421.12777. Epub 2020 Feb 25.
• [11] Contribution of Altered Endocannabinoid System to Overactive mTORC1 Signaling in Focal Cortical Dysplasia. Front Pharmacol. 2019 Jan 9;9:1508. doi: 10.3389/fphar.2018.01508. eCollection 2018.