Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT23T37S)

• DOT Name: Bone morphogenetic protein 2 (BMP2)
• Synonyms: BMP-2; Bone morphogenetic protein 2A; BMP-2A
• Gene Name: BMP2
• Related Disease:
  Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1
  Brachydactyly type A2
• UniProt ID: BMP2_HUMAN
• PDB ID: 1ES7; 1REU; 1REW; 2GOO; 2H62; 2H64; 2QJ9; 2QJA; 2QJB; 3BK3; 3BMP; 4MID; 4N1D; 4UHY; 4UHZ; 4UI0; 4UI1; 4UI2; 6OMN; 7AG0; 8E3G
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MVAGTRCLLALLLPQVLLGGAAGLVPELGRRKFAAASSGRPSSQPSDEVLSEFELRLLSM
  FGLKQRPTPSRDAVVPPYMLDLYRRHSGQPGSPAPDHRLERAASRANTVRSFHHEESLEE
  LPETSGKTTRRFFFNLSSIPTEEFITSAELQVFREQMQDALGNNSSFHHRINIYEIIKPA
  TANSKFPVTRLLDTRLVNQNASRWESFDVTPAVMRWTAQGHANHGFVVEVAHLEEKQGVS
  KRHVRISRSLHQDEHSWSQIRPLLVTFGHDGKGHPLHKREKRQAKHKQRKRLKSSCKRHP
  LYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKAC
  CVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR
• Function: Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Also acts to promote expression of HAMP, via the interaction with its receptor BMPR1A/ALK3. Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation. Also stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling.
• Tissue Specificity: Particularly abundant in lung, spleen and colon and in low but significant levels in heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, prostate, ovary and small intestine.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Hippo sig.ling pathway (hsa04390)
  Pathways in cancer (hsa05200)
  Basal cell carcinoma (hsa05217)
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  Transcriptional regulation by RUNX2 (R-HSA-8878166)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  Signaling by BMP (R-HSA-201451)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1	DISYVCNF	Strong	Autosomal dominant	[1]
Brachydactyly type A2	DISUB1OU	Supportive	Autosomal dominant	[2]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Bone morphogenetic protein 2 (BMP2) increases the abundance of Estradiol.	[36]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Bone morphogenetic protein 2 (BMP2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Bone morphogenetic protein 2 (BMP2).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Bone morphogenetic protein 2 (BMP2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bone morphogenetic protein 2 (BMP2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Bone morphogenetic protein 2 (BMP2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Bone morphogenetic protein 2 (BMP2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Bone morphogenetic protein 2 (BMP2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Bone morphogenetic protein 2 (BMP2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Bone morphogenetic protein 2 (BMP2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Bone morphogenetic protein 2 (BMP2).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Bone morphogenetic protein 2 (BMP2).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Bone morphogenetic protein 2 (BMP2).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Bone morphogenetic protein 2 (BMP2).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Bone morphogenetic protein 2 (BMP2).	[15]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Bone morphogenetic protein 2 (BMP2).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Bone morphogenetic protein 2 (BMP2).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Bone morphogenetic protein 2 (BMP2).	[17]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Bone morphogenetic protein 2 (BMP2).	[18]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Bone morphogenetic protein 2 (BMP2).	[19]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Bone morphogenetic protein 2 (BMP2).	[20]
Phosphate	DMUXQG7	Approved	Phosphate increases the expression of Bone morphogenetic protein 2 (BMP2).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Bone morphogenetic protein 2 (BMP2).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Bone morphogenetic protein 2 (BMP2).	[22]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Bone morphogenetic protein 2 (BMP2).	[23]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Bone morphogenetic protein 2 (BMP2).	[24]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Bone morphogenetic protein 2 (BMP2).	[25]
ICARIIN	DMOJQGT	Phase 3	ICARIIN increases the expression of Bone morphogenetic protein 2 (BMP2).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Bone morphogenetic protein 2 (BMP2).	[27]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Bone morphogenetic protein 2 (BMP2).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Bone morphogenetic protein 2 (BMP2).	[30]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Bone morphogenetic protein 2 (BMP2).	[16]
Mevastatin	DM1LGKP	Terminated	Mevastatin increases the expression of Bone morphogenetic protein 2 (BMP2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Bone morphogenetic protein 2 (BMP2).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Bone morphogenetic protein 2 (BMP2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Bone morphogenetic protein 2 (BMP2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Bone morphogenetic protein 2 (BMP2).	[32]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Bone morphogenetic protein 2 (BMP2).	[33]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Bone morphogenetic protein 2 (BMP2).	[34]
Cordycepin	DM72Y01	Investigative	Cordycepin affects the expression of Bone morphogenetic protein 2 (BMP2).	[20]
NAPQI	DM8F5LR	Investigative	NAPQI increases the expression of Bone morphogenetic protein 2 (BMP2).	[35]
VITAMIN K2	DMJB3E1	Investigative	VITAMIN K2 increases the expression of Bone morphogenetic protein 2 (BMP2).	[21]

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