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

General Information of Drug (ID: DMTM4QA)

• Drug Name: LCL161 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Phase 2	[1]
Myelofibrosis	2A20.2	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Breast cancer	2C60-2C65	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 24737642
  CAS Number: CAS 1005342-46-0
  TTD Drug ID: DMTM4QA

Molecule-Related Drug Atlas

Drug(s) Targeting Inhibitor of apoptosis protein (hIAP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT-406	DMVJW0S	Squamous head and neck cell carcinom	2D60.0	Phase 3	[5]
APG-1387	DMLEKUY	Haematological malignancy	2B33.Y	Phase 1	[1]

Drug(s) Affected By Baculoviral IAP repeat-containing protein 5 (BIRC5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[6]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[7]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[8]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[9]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[10]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[11]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[12]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[15]

Drug(s) Affected By Baculoviral IAP repeat-containing protein 2 (BIRC2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[16]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[17]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[20]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[21]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Trovafloxacin	DM6AN32	Acute gonococcal cervicitis		Approved	[23]
Etodolac	DM6WJO9	Osteoarthritis	FA00-FA05	Approved	[24]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Inhibitor of apoptosis protein (hIAP)	TTS74QB	XIAP_HUMAN; BIRC2_HUMAN; BIRC3_HUMAN; BIRC1_HUMAN; BIRC7_HUMAN; BIRC5_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Gene/Protein Processing	[4]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[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: 7912).
• [3] National Cancer Institute Drug Dictionary (drug id 670651).
• [4] The SMAC mimetic LCL161 is a direct ABCB1/MDR1-ATPase activity modulator and BIRC5/Survivin expression down-regulator in cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115080. doi: 10.1016/j.taap.2020.115080. Epub 2020 Jun 1.
• [5] 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: 7729).
• [6] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [7] Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
• [8] Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines. J Biochem Mol Toxicol. 2021 Jun;35(6):1-11. doi: 10.1002/jbt.22770. Epub 2021 Mar 11.
• [9] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [10] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [11] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [12] Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin. Invest New Drugs. 2011 Oct;29(5):945-52. doi: 10.1007/s10637-010-9450-2. Epub 2010 May 13.
• [13] Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene. 2005 Sep 15;24(41):6213-21. doi: 10.1038/sj.onc.1208774.
• [14] Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway. Cancer Invest. 2009 Jul;27(6):604-12. doi: 10.1080/07357900802337191.
• [15] Troglitazone sensitizes tumor cells to TRAIL-induced apoptosis via down-regulation of FLIP and Survivin. Apoptosis. 2006 Sep;11(9):1503-12. doi: 10.1007/s10495-006-8896-3.
• [16] Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes non-Hodgkin's lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis. Mol Cancer Ther. 2004 Jan;3(1):71-84.
• [17] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
• [18] Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer. 2008 Aug 15;123(4):951-7. doi: 10.1002/ijc.23593.
• [19] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [20] Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
• [21] The antipsychotic chlorpromazine suppresses YAP signaling, stemness properties, and drug resistance in breast cancer cells. Chem Biol Interact. 2019 Apr 1;302:28-35. doi: 10.1016/j.cbi.2019.01.033. Epub 2019 Jan 28.
• [22] Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO). Int J Biochem Cell Biol. 2019 Nov;116:105615. doi: 10.1016/j.biocel.2019.105615. Epub 2019 Sep 17.
• [23] The hepatotoxic fluoroquinolone trovafloxacin disturbs TNF- and LPS-induced p65 nuclear translocation in vivo and in vitro. Toxicol Appl Pharmacol. 2020 Mar 15;391:114915. doi: 10.1016/j.taap.2020.114915. Epub 2020 Feb 6.
• [24] Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells. Eur J Haematol. 2005 Sep;75(3):212-20. doi: 10.1111/j.1600-0609.2005.00498.x.
• [25] Apoptosis induction by 1alpha,25-dihydroxyvitamin D3 in prostate cancer. Mol Cancer Ther. 2002 Jul;1(9):667-77.