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

General Information of Drug (ID: DMPFLS5)

• Drug Name: ABT-100 Drug Info
• Synonyms: A-367074; A-409100; A-367074.1

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 6451154
  ChEBI ID: CHEMBL4586794
  CAS Number: CAS 450839-40-4
  TTD Drug ID: DMPFLS5

Molecule-Related Drug Atlas

Drug(s) Targeting CAAX farnesyltransferase beta (FNTB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]
ABT-839	DM4UN9A	Non-small-cell lung cancer	2C25.Y	Terminated	[5]
MANUMYCIN A	DM1SWOY	N. A.	N. A.	Terminated	[6]
SCH-44342	DMUL4VX	N. A.	N. A.	Terminated	[4]
RPR-113829	DMJ63GW	N. A.	N. A.	Terminated	[7]
RPR-114334	DMAIJT6	N. A.	N. A.	Terminated	[7]
L-731735	DM1XBKC	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]
FUSIDIENOL	DMI1Y92	N. A.	N. A.	Terminated	[8]
B-956	DM1IO9X	Solid tumour/cancer	2A00-2F9Z	Terminated	[9]
L-739749	DMAUG0L	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]

Drug(s) Affected By Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[10]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[11]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[16]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]

Drug(s) Affected By Cyclin-dependent kinase inhibitor 1B (CDKN1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[21]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[24]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[27]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CAAX farnesyltransferase beta (FNTB)	TT7WZIJ	FNTB_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Post-Translational Modifications	[3]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Post-Translational Modifications	[3]

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 800019239)
• [2] Potent farnesyltransferase inhibitor ABT-100 abrogates acute allograft rejection. J Heart Lung Transplant. 2005 Sep;24(9):1403-9.
• [3] Farnesyltransferase inhibitor, ABT-100, is a potent liver cancer chemopreventive agent. Clin Cancer Res. 2005 Jun 1;11(11):4266-74. doi: 10.1158/1078-0432.CCR-04-2386.
• [4] Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
• [5] Design and synthesis of o-trifluoromethylbiphenyl substituted 2-amino-nicotinonitriles as inhibitors of farnesyltransferase. Bioorg Med Chem Lett. 2005 Jan 3;15(1):153-8.
• [6] A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
• [7] Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
• [8] Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking. J Med Chem. 2002 Mar 28;45(7):1460-5.
• [9] Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res. 1995 Nov 15;55(22):5310-4.
• [10] Repression of Kisspeptin1 weakens hydrogen peroxide-caused injury in HTR8 cells via adjusting PI3K/AKT/mTOR pathway. J Biochem Mol Toxicol. 2020 May;34(5):e22461. doi: 10.1002/jbt.22461. Epub 2020 Feb 11.
• [11] Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol Biol Rep. 2015 Sep;42(9):1419-29. doi: 10.1007/s11033-015-3921-7. Epub 2015 Aug 27.
• [12] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [13] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [14] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [15] Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells. Environ Toxicol. 2021 Sep;36(9):1785-1792. doi: 10.1002/tox.23299. Epub 2021 May 27.
• [16] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [17] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [18] A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3378-83.
• [19] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [20] Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011 Apr 28;18(3):333-45. doi: 10.1530/ERC-10-0262. Print 2011 Jun.
• [21] Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival. Cancer Res. 2006 Jun 1;66(11):5542-8. doi: 10.1158/0008-5472.CAN-05-4620.
• [22] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [23] Methotrexate increases expression of cell cycle checkpoint genes via JNK activation. Arthritis Rheum. 2012 Jun;64(6):1780-9. doi: 10.1002/art.34342. Epub 2011 Dec 19.
• [24] Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells. Melanoma Res. 2008 Apr;18(2):85-94. doi: 10.1097/CMR.0b013e3282f60097.
• [25] The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res. 2005 Jan 1;65(1):18-25.
• [26] Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol. 2001 May 15;61(10):1205-15. doi: 10.1016/s0006-2952(01)00583-4.
• [27] Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1. Biochem Pharmacol. 2008 May 15;75(10):1924-34. doi: 10.1016/j.bcp.2008.02.013. Epub 2008 Feb 17.
• [28] Induction mechanism of apoptosis by troglitazone through peroxisome proliferator-activated receptor-gamma in gastric carcinoma cells. Anticancer Res. 2003 Jan-Feb;23(1A):267-73.
• [29] Down-regulation of CD44 contributes to the differentiation of HL-60 cells induced by ATRA or HMBA. Cell Mol Immunol. 2007 Feb;4(1):59-63.