Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWRYSNA)

• DOT Name: Bcl-2-related protein A1 (BCL2A1)
• Synonyms: Bcl-2-like protein 5; Bcl2-L-5; Hemopoietic-specific early response protein; Protein BFL-1; Protein GRS
• Gene Name: BCL2A1
• UniProt ID: B2LA1_HUMAN
• PDB ID: 2VM6; 3I1H; 3MQP; 4ZEQ; 5UUK; 5UUL; 5UUP; 5WHH; 5WHI; 6E3I; 6E3J; 6MBB; 6MBC; 6RJP; 6VO4
• Pfam ID: PF00452
• Sequence:
  MTDCEFGYIYRLAQDYLQCVLQIPQPGSGPSKTSRVLQNVAFSVQKEVEKNLKSCLDNVN
  VVSVDTARTLFNQVMEKEFEDGIINWGRIVTIFAFEGILIKKLLRQQIAPDVDTYKEISY
  FVAEFIMNNTGEWIRQNGGWENGFVKKFEPKSGWMTFLEVTGKICEMLSLLKQYC
• Function: Retards apoptosis induced by IL-3 deprivation. May function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection. Can inhibit apoptosis induced by serum starvation in the mammary epithelial cell line HC11.
• Tissue Specificity: Seems to be restricted to the hematopoietic compartment. Expressed in peripheral blood, spleen, and bone marrow, at moderate levels in lung, small intestine and testis, at a minimal levels in other tissues. Also found in vascular smooth muscle cells and hematopoietic malignancies.
• KEGG Pathway:
  NF-kappa B sig.ling pathway (hsa04064)
  Apoptosis (hsa04210)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
• Reactome Pathway: Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Bcl-2-related protein A1 (BCL2A1) decreases the response to substance of Methotrexate.	[31]

37 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bcl-2-related protein A1 (BCL2A1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bcl-2-related protein A1 (BCL2A1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Bcl-2-related protein A1 (BCL2A1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Bcl-2-related protein A1 (BCL2A1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Bcl-2-related protein A1 (BCL2A1).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[10]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[10]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[11]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[12]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Bcl-2-related protein A1 (BCL2A1).	[13]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[14]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[10]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Bcl-2-related protein A1 (BCL2A1).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Bcl-2-related protein A1 (BCL2A1).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[17]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[18]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Bcl-2-related protein A1 (BCL2A1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[20]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Bcl-2-related protein A1 (BCL2A1).	[21]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[22]
M-carboxycinnamic acid bishydroxamide	DMHJLPS	Preclinical	M-carboxycinnamic acid bishydroxamide decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Bcl-2-related protein A1 (BCL2A1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Bcl-2-related protein A1 (BCL2A1).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Bcl-2-related protein A1 (BCL2A1).	[26]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Bcl-2-related protein A1 (BCL2A1).	[27]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Bcl-2-related protein A1 (BCL2A1).	[21]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Bcl-2-related protein A1 (BCL2A1).	[28]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Bcl-2-related protein A1 (BCL2A1).	[29]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Bcl-2-related protein A1 (BCL2A1).	[30]

References

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• [12] Effect of indomethacin on Bfl-1, WISP-1 and proliferating cell nuclear antigen in colon cancer cell line HCT116 cells. Chin J Dig Dis. 2006;7(4):219-24. doi: 10.1111/j.1443-9573.2006.00272.x.
• [13] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [14] Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFalpha/NF-kappaB signaling axis. Leukemia. 2010 Aug;24(8):1476-86. doi: 10.1038/leu.2010.117. Epub 2010 Jun 3.
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• [17] Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem. 2007 Jul;102(2):522-38. doi: 10.1111/j.1471-4159.2007.04633.x.
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• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
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• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
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• [27] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.
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