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

General Information of Drug (ID: DMDE8YS)

• Drug Name: TW-37 Drug Info
• Synonyms: TW-37; 877877-35-5; N-[4-(2-tert-Butylphenylsulfonyl)phenyl]-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide; tw 37; CHEMBL217354; N-(4-((2-(tert-butyl)phenyl)sulfonyl)phenyl)-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide; N-(4-(2-tert-butylphenylsulfonyl)phenyl)-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide; N-[4-[(2-tert-Butylphenyl)sulfonyl]phenyl]-2,3,4-trihydroxy-5-[(2-isopropylphenyl)methyl]benzamide; N-(4-((2-Tert-Butylphenyl)sulfonyl)phenyl)-2,3,4-trihydroxy-5-((2-isopropylphenyl)methyl)benzamide

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 11455910
  ChEBI ID: CHEBI:95008
  CAS Number: CAS 877877-35-5
  TTD Drug ID: DMDE8YS

Molecule-Related Drug Atlas

Drug(s) Targeting Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Obatoclax	DMPF9ZM	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
AZD5991	DM7QGHO	Haematological malignancy	2B33.Y	Phase 1	[4]
AMG 176	DM0Q7NO	Acute myeloid leukaemia	2A60	Phase 1	[4]
PRT1419	DMIKE0O	Melanoma	2C30	Phase 1	[5]
ABBV-467	DM87SM9	Multiple myeloma	2A83	Phase 1	[6]
MIK665	DMTUVCG	Acute myeloid leukaemia	2A60	Phase 1	[7]
AMG 397	DM7CNTG	Refractory hematologic malignancy	2A85.5	Phase 1	[8]
PMID27744724-Compound-18	DM73S2C	N. A.	N. A.	Patented	[9]
Indole-based analog 2	DM0NEVC	N. A.	N. A.	Patented	[9]
PMID27744724-Compound-10	DMFKS2P	N. A.	N. A.	Patented	[9]

Drug(s) Targeting Bcl-x messenger RNA (BCL2L1 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PURPUROGALLIN	DM63O4F	N. A.	N. A.	Terminated	[10]
QEDIIRNIARHLAQVGDSMDR	DMJ38YV	Discovery agent	N.A.	Investigative	[1]
4,5-dibenzylbenzene-1,2-diol	DMHURXY	Discovery agent	N.A.	Investigative	[11]
ISIS 11219	DMW3145	Discovery agent	N.A.	Investigative	[12]
ISIS 11220	DMNJS0K	Discovery agent	N.A.	Investigative	[12]
ISIS 11224	DMMGA6K	Discovery agent	N.A.	Investigative	[12]
ISIS 11223	DM7LPI4	Discovery agent	N.A.	Investigative	[12]
ISIS 16010	DMZID0W	Discovery agent	N.A.	Investigative	[12]
ISIS 16009	DMBRKFC	Discovery agent	N.A.	Investigative	[12]
ISIS 15998	DMAQ9EB	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Apoptosis regulator Bcl-2 (BCL-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MCI-186	DM8ZHP1	Amyotrophic lateral sclerosis	8B60.0	Approved	[13]
Taxol	DMUOT9V	Breast cancer	2C60-2C65	Approved	[14]
GDC-0199	DMH0QKA	Chronic lymphocytic leukaemia	2A82.0	Approved	[15]
ABT-263	DMNE56X	Myelofibrosis	2A20.2	Phase 3	[16]
Taxol/Paraplatin/Herceptin	DML6GAN	Breast cancer	2C60-2C65	Phase 3	[17]
Oblimersen	DM7KI4E	Melanoma	2C30	Phase 3	[18]
RG7601	DMDVAFP	Chronic lymphocytic leukaemia	2A82.0	Phase 3	[15]
Thymoquinone	DMVDTR2	Polycystic ovarian syndrome	5A80.1	Phase 2/3	[19]
Obatoclax	DMPF9ZM	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
PI-88/Taxotere	DM4FIWC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Inhibitor	[1]
Bcl-x messenger RNA (BCL2L1 mRNA)	TTRE6AX	B2CL1_HUMAN	Inhibitor	[2]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	TTL53M6	MCL1_HUMAN	Inhibitor	[1]

References

• [1] Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem. 2006 Oct 19;49(21):6139-42.
• [2] Fragment-based deconstruction of Bcl-xL inhibitors. J Med Chem. 2010 Mar 25;53(6):2577-88.
• [3] 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.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of Prelude Therapeutics.
• [6] Clinical pipeline report, company report or official report of AbbVie.
• [7] MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells. Cell Death Dis. 2020 Jun 8;11(6):443.
• [8] Clinical pipeline report, company report or official report of Amgen.
• [9] Mcl-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Feb;27(2):163-178.
• [10] Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem. 2003 Sep 25;46(20):4259-64.
• [11] Vaccinia virus virulence factor N1L is a novel promising target for antiviral therapeutic intervention. J Med Chem. 2010 May 27;53(10):3899-906.
• [12] US patent application no. 7,148,204, Antisense modulation of bcl-x expression.
• [13] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [14] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [15] ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.
• [16] Clinical pipeline report, company report or official report of Roche (2009).
• [17] 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.
• [18] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [19] 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.
• [20] 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.