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

General Information of DTT (ID: TTJGNVC)

• DTT Name: Apoptosis regulator Bcl-2 (BCL-2) DTT Info
• Gene Name: BCL2

Molecule-Related Drug & Molecule List

3 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GDC-0199	DMH0QKA	Chronic lymphocytic leukaemia	2A82.0	Approved	[1]
MCI-186	DM8ZHP1	Amyotrophic lateral sclerosis	8B60.0	Approved	[2]
Taxol	DMUOT9V	Breast cancer	2C60-2C65	Approved	[3]

18 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-263	DMNE56X	Myelofibrosis	2A20.2	Phase 3	[4]
Oblimersen	DM7KI4E	Melanoma	2C30	Phase 3	[5]
RG7601	DMDVAFP	Chronic lymphocytic leukaemia	2A82.0	Phase 3	[1]
Taxol/Paraplatin/Herceptin	DML6GAN	Breast cancer	2C60-2C65	Phase 3	[6]
Thymoquinone	DMVDTR2	Polycystic ovarian syndrome	5A80.1	Phase 2/3	[7]
Gossypol	DMJWE3I	Prostate cancer	2C82.0	Phase 2	[8]
Obatoclax	DMPF9ZM	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
PI-88/Taxotere	DM4FIWC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
APG-1252	DM8O3R9	Small-cell lung cancer	2C25.Y	Phase 1/2	[11]
APG-2575	DMPWBM2	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[12]
AZD0466	DMWLZI6	Hematologic tumour	2B33.Y	Phase 1/2	[13]
AI-850	DMDA1UB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
BCL201	DMZ51EX	Follicular lymphoma	2A80	Phase 1	[15]
BGB-11417	DM7QTIC	Acute myeloid leukaemia	2A60	Phase 1	[16]
LOXO-338	DMPX2ZR	Haematological malignancy	2B33.Y	Phase 1	[17]
LP-108	DMYIXQZ	Acute myeloid leukaemia	2A60	Phase 1	[18]
Pc4	DM23K45	Psoriasis vulgaris	EA90	Phase 1	[19]
VOB560	DMDG30Q	Acute myeloid leukaemia	2A60	Phase 1	[20]

5 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indole-based analog 2	DM0NEVC	N. A.	N. A.	Patented	[21]
Indole-based analog 3	DMTEYQJ	N. A.	N. A.	Patented	[21]
PMID27744724-Compound-10	DMFKS2P	N. A.	N. A.	Patented	[21]
PMID27744724-Compound-18	DM73S2C	N. A.	N. A.	Patented	[21]
PMID27744724-Compound-21	DM18UA5	N. A.	N. A.	Patented	[21]

1 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-737	DML0DBV	N. A.	N. A.	Terminated	[22]

9 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,3,4-trihydroxy-5-isopropyl-N-phenyl-benzamide	DMCAZ32	Discovery agent	N.A.	Investigative	[23]
4,5-dibenzylbenzene-1,2-diol	DMHURXY	Discovery agent	N.A.	Investigative	[24]
5,10-Dioxy-2-phenyl-benzo[g]pteridin-4-ylamine	DMM7N6K	Discovery agent	N.A.	Investigative	[25]
Apogossypol	DM7OPCH	Solid tumour/cancer	2A00-2F9Z	Investigative	[26]
modified HA14-1 compounds (cancer)	DMB5OG8	Discovery agent	N.A.	Investigative	[27]
N-phenyl-2,3,4-trihydroxy-5-benzyl-benzamide	DM0JI2L	Discovery agent	N.A.	Investigative	[23]
QEDIIRNIARHLAQVGDSMDR	DMJ38YV	Discovery agent	N.A.	Investigative	[23]
TW-37	DMDE8YS	Discovery agent	N.A.	Investigative	[23]
WL-276	DM8SEHO	Solid tumour/cancer	2A00-2F9Z	Investigative	[28]

References

• [1] ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.
• [2] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [3] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [4] Clinical pipeline report, company report or official report of Roche (2009).
• [5] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [6] Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32.
• [7] Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197.
• [8] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [9] Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9.
• [10] Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer. Ann Oncol. 2010 Jun;21(6):1302-7.
• [11] Bcl-2/Bcl-xl inhibitor APG-1252-M1 is a promising therapeutic strategy for gastric carcinoma. Cancer Med. 2020 Jun;9(12):4197-4206.
• [12] A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma. Oncol Res. 2020 Sep 1;28(4):331-344.
• [13] Design and optimisation of dendrimer-conjugated Bcl-2/x L inhibitor, AZD0466, with improved therapeutic index for cancer therapy. Commun Biol. 2021 Jan 25;4(1):112.
• [14] Intravenous hydrophobic drug delivery: a porous particle formulation of paclitaxel (AI-850). Pharm Res. 2005 Mar;22(3):347-55.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Clinical pipeline report, company report or official report of BeiGene.
• [17] ClinicalTrials.gov (NCT05024045) A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies. U.S.National Institutes of Health.
• [18] National Cancer Institute Drug Dictionary (drug name LP-108).
• [19] Association between the photodynamic loss of Bcl-2 and the sensitivity to apoptosis caused by phthalocyanine photodynamic therapy. Photochem Photobiol. 2003 Jul;78(1):1-8.
• [20] Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer. Cells. 2020 May 21;9(5):1287.
• [21] Mcl-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Feb;27(2):163-178.
• [22] Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J Med Chem. 2007 Feb 22;50(4):641-62.
• [23] Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem. 2006 Oct 19;49(21):6139-42.
• [24] Vaccinia virus virulence factor N1L is a novel promising target for antiviral therapeutic intervention. J Med Chem. 2010 May 27;53(10):3899-906.
• [25] Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening. J Med Chem. 2001 Dec 6;44(25):4313-24.
• [26] 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: 7920).
• [27] The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism. Mol Cancer Ther. 2004 Dec;3(12):1513-24.
• [28] WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth. Cancer Res. 2008 Jun 1;68(11):4377-83.