Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4JGYU)

• DOT Name: Alpha-crystallin B chain (CRYAB)
• Synonyms: Alpha(B)-crystallin; Heat shock protein beta-5; HspB5; Renal carcinoma antigen NY-REN-27; Rosenthal fiber component
• Gene Name: CRYAB
• Related Disease:
  Cataract 16 multiple types
  Fatal infantile hypertonic myofibrillar myopathy
  Myofibrillar myopathy 2
  Early-onset lamellar cataract
  Early-onset nuclear cataract
  Early-onset posterior polar cataract
  Obsolete familial isolated dilated cardiomyopathy
  Dilated cardiomyopathy 1II
• UniProt ID: CRYAB_HUMAN
• PDB ID: 2KLR; 2N0K; 2WJ7; 2Y1Y; 2Y1Z; 2Y22; 2YGD; 3J07; 3L1G; 3SGM; 3SGN; 3SGO; 3SGP; 3SGR; 3SGS; 4M5S; 4M5T; 5VVV; 6BP9; 7ROJ
• Pfam ID: PF00525 ; PF00011
• Sequence:
  MDIAIHHPWIRRPFFPFHSPSRLFDQFFGEHLLESDLFPTSTSLSPFYLRPPSFLRAPSW
  FDTGLSEMRLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHR
  KYRIPADVDPLTITSSLSSDGVLTVNGPRKQVSGPERTIPITREEKPAVTAAPKK
• Function: May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial cells, stabilizes the ATP6V1A protein, preventing its degradation by the proteasome.
• Tissue Specificity: Lens as well as other tissues . Expressed in myocardial tissue .
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Longevity regulating pathway - multiple species (hsa04213)
• Reactome Pathway: HSF1-dependent transactivation (R-HSA-3371571)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 16 multiple types	DIS6W7YF	Strong	Autosomal recessive	[1]
Fatal infantile hypertonic myofibrillar myopathy	DISK4LYQ	Strong	Autosomal recessive	[2]
Myofibrillar myopathy 2	DIS5BABS	Strong	Autosomal dominant	[3]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[4]
Early-onset nuclear cataract	DISGIHUY	Supportive	Autosomal dominant	[1]
Early-onset posterior polar cataract	DISJFK9W	Supportive	Autosomal dominant	[5]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[6]
Dilated cardiomyopathy 1II	DISUHXLH	Limited	Autosomal dominant	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Alpha-crystallin B chain (CRYAB) decreases the response to substance of Doxorubicin.	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Alpha-crystallin B chain (CRYAB).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alpha-crystallin B chain (CRYAB).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alpha-crystallin B chain (CRYAB).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-crystallin B chain (CRYAB).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha-crystallin B chain (CRYAB).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-crystallin B chain (CRYAB).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alpha-crystallin B chain (CRYAB).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-crystallin B chain (CRYAB).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Alpha-crystallin B chain (CRYAB).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Alpha-crystallin B chain (CRYAB).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Alpha-crystallin B chain (CRYAB).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alpha-crystallin B chain (CRYAB).	[19]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Alpha-crystallin B chain (CRYAB).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Alpha-crystallin B chain (CRYAB).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Alpha-crystallin B chain (CRYAB).	[21]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Alpha-crystallin B chain (CRYAB).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Alpha-crystallin B chain (CRYAB).	[23]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Alpha-crystallin B chain (CRYAB).	[24]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Alpha-crystallin B chain (CRYAB).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Alpha-crystallin B chain (CRYAB).	[26]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Alpha-crystallin B chain (CRYAB).	[27]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of Alpha-crystallin B chain (CRYAB).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Alpha-crystallin B chain (CRYAB).	[29]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Alpha-crystallin B chain (CRYAB).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Alpha-crystallin B chain (CRYAB).	[31]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Alpha-crystallin B chain (CRYAB).	[32]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Alpha-crystallin B chain (CRYAB).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alpha-crystallin B chain (CRYAB).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Alpha-crystallin B chain (CRYAB).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Alpha-crystallin B chain (CRYAB).	[36]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Alpha-crystallin B chain (CRYAB).	[37]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Alpha-crystallin B chain (CRYAB).	[38]

References

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• [2] AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci. 2001 Nov;42(12):2924-34.
• [3] Mutation R120G in alphaB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6137-42. doi: 10.1073/pnas.96.11.6137.
• [4] A novel alphaB-crystallin mutation associated with autosomal dominant congenital lamellar cataract. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1069-75. doi: 10.1167/iovs.05-1004.
• [5] Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3461-6. doi: 10.1167/iovs.05-1438.
• [6] Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem Biophys Res Commun. 2006 Apr 7;342(2):379-86. doi: 10.1016/j.bbrc.2006.01.154. Epub 2006 Feb 8.
• [7] Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann Neurol. 2003 Dec;54(6):804-10. doi: 10.1002/ana.10767.
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• [13] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
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• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Effect of topical Ginkgo biloba extract on steroid-induced changes in the trabecular meshwork and intraocular pressure. Arch Ophthalmol. 2008 Dec;126(12):1700-6. doi: 10.1001/archophthalmol.2008.512.
• [23] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [24] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [25] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [26] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [27] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [28] The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis. Redox Biol. 2020 Sep;36:101594. doi: 10.1016/j.redox.2020.101594. Epub 2020 May 29.
• [29] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [30] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
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• [32] Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
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• [37] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
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• [39] cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat. 2006 Mar;96(1):17-39. doi: 10.1007/s10549-005-9026-6. Epub 2005 Dec 2.