Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX14BAS)

DOT Name	CASP8 and FADD-like apoptosis regulator (CFLAR)
Synonyms	Caspase homolog; CASH; Caspase-eight-related protein; Casper; Caspase-like apoptosis regulatory protein; CLARP; Cellular FLICE-like inhibitory protein; c-FLIP; FADD-like antiapoptotic molecule 1; FLAME-1; Inhibitor of FLICE; I-FLICE; MACH-related inducer of toxicity; MRIT; Usurpin
Gene Name	CFLAR
UniProt ID	CFLAR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2N5R; 3H11; 3H13; 6M6O; 7DEE; 7LXC
Pfam ID	PF01335 ; PF00656
Sequence	MSAEVIHQVEEALDTDEKEMLLFLCRDVAIDVVPPNVRDLLDILRERGKLSVGDLAELLY RVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGEDLDKSDVSSLIFLMKDYM GRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIHRIDLKTKIQKYKQSVQGAGT SYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLGAQQEPVKKSIQESEAFLPQSIP EERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP EHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLHHIRRMFMGDSCPYLAGKPKMFFIQNY VVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGLCTVHREADFFWSLCTADMSLLEQSHSSP SLYLQCLSQKLRQERKRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT
Function	Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity.
Tissue Specificity	Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.
KEGG Pathway	NF-kappa B sig.ling pathway (hsa04064 ) Autophagy - animal (hsa04140 ) Apoptosis (hsa04210 ) Necroptosis (hsa04217 ) TNF sig.ling pathway (hsa04668 ) Chagas disease (hsa05142 ) Hepatitis C (hsa05160 )
Reactome Pathway	CASP8 activity is inhibited (R-HSA-5218900 ) TRAIL signaling (R-HSA-75158 ) RIPK1-mediated regulated necrosis (R-HSA-5213460 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	CASP8 and FADD-like apoptosis regulator (CFLAR) decreases the response to substance of Paclitaxel.	[64]
Pemetrexed	DMMX2E6	Approved	CASP8 and FADD-like apoptosis regulator (CFLAR) decreases the response to substance of Pemetrexed.	[65]
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65 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[14]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[19]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[20]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[21]
Aspirin	DM672AH	Approved	Aspirin increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[22]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[4]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[23]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[10]
Menthol	DMG2KW7	Approved	Menthol increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[24]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[25]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[26]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[27]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[28]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[29]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[30]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[31]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[32]
Adenosine	DMM2NSK	Approved	Adenosine decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[33]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[34]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[35]
Ibrutinib	DMHZCPO	Approved	Ibrutinib decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[37]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[39]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[40]
I3C	DMIGFOR	Phase 3	I3C decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[41]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[42]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[43]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[46]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[47]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[48]
PMID28870136-Compound-49	DMTUC9E	Patented	PMID28870136-Compound-49 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[49]
MG-132	DMKA2YS	Preclinical	MG-132 affects the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[54]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[55]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[56]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[57]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[58]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[59]
gingerol	DMNXYSM	Investigative	gingerol decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[60]
BAY11-7082	DMQNOFA	Investigative	BAY11-7082 decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[7]
Hyperforin	DM2L3PE	Investigative	Hyperforin decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[61]
droxinostat	DM5IA9W	Investigative	droxinostat decreases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[62]
lysophosphatidylethanolamine	DMI4FKH	Investigative	lysophosphatidylethanolamine increases the expression of CASP8 and FADD-like apoptosis regulator (CFLAR).	[63]
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⏷ Show the Full List of 65 Drug(s)

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the cleavage of CASP8 and FADD-like apoptosis regulator (CFLAR).	[38]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CASP8 and FADD-like apoptosis regulator (CFLAR).	[45]
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65	Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed-induced apoptosis in human lung cancer cells. Eur J Cancer. 2011 Nov;47(16):2471-8. doi: 10.1016/j.ejca.2011.06.003. Epub 2011 Jul 2.