Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI1JF13)

• DOT Name: Parathyroid hormone-related protein (PTHLH)
• Synonyms: PTH-rP; PTHrP; Parathyroid hormone-like protein; PLP) ; PTHrP; Osteostatin (PTHrP)]
• Gene Name: PTHLH
• Related Disease:
  Bone resorption
  Brachydactyly type E2
  Glioma
  Melanoma
  Metastatic malignant neoplasm
  Achondroplasia
  Bone osteosarcoma
  Breast carcinoma
  Carcinoma
  Chondrosarcoma
  Chronic pancreatitis
  Chronic renal failure
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  End-stage renal disease
  Lung squamous cell carcinoma
  Neuroblastoma
  Non-small-cell lung cancer
  Osteoarthritis
  Osteoporosis
  Osteosarcoma
  Pancreatic tumour
  Plasma cell myeloma
  Postmenopausal osteoporosis
  Primary hyperparathyroidism
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Rheumatoid arthritis
  Squamous cell carcinoma
  Trichohepatoenteric syndrome
  Nervous system inflammation
  Paraneoplastic syndrome
  Brachydactyly type E
  Hereditary spastic paraplegia 2
  Lung neoplasm
  T-cell leukaemia
  Brachydactyly
  Neuroendocrine neoplasm
  Prostate cancer
  Pseudohypoparathyroidism type 1B
  Pulmonary disease
  Type-1/2 diabetes
• UniProt ID: PTHR_HUMAN
• PDB ID: 1BZG; 1M5N; 3FFD; 3H3G; 7UZO; 7UZP; 7VVJ; 8D51; 8D52; 8FLR; 8HAF
• Pfam ID: PF01279
• Sequence:
  MQRRLVQQWSVAVFLLSYAVPSCGRSVEGLSRRLKRAVSEHQLLHDKGKSIQDLRRRFFL
  HHLIAEIHTAEIRATSEVSPNSKPSPNTKNHPVRFGSDDEGRYLTQETNKVETYKEQPLK
  TPGKKKKGKPGKRKEQEKKKRRTRSAWLDSGVTGSGLEGDHLSDTSTTSLELDSRRH
• Function: Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Up-regulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath. Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1; Osteostatin is a potent inhibitor of osteoclastic bone resorption.
• Tissue Specificity: Ubiquitous. Also expressed in the mammary gland.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone resorption	DISGSZ65	Definitive	Biomarker	[1]
Brachydactyly type E2	DISLZDCE	Definitive	Autosomal dominant	[2]
Glioma	DIS5RPEH	Definitive	Biomarker	[3]
Melanoma	DIS1RRCY	Definitive	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[5]
Achondroplasia	DISYWN2O	Strong	Altered Expression	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Biomarker	[9]
Chondrosarcoma	DIS4I7JB	Strong	Altered Expression	[10]
Chronic pancreatitis	DISBUOMJ	Strong	Biomarker	[11]
Chronic renal failure	DISGG7K6	Strong	Altered Expression	[12]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Altered Expression	[14]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[14]
End-stage renal disease	DISXA7GG	Strong	Altered Expression	[12]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[15]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[18]
Osteoporosis	DISF2JE0	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[21]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[22]
Primary hyperparathyroidism	DISB4U1Q	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[13]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[26]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[27]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[28]
Nervous system inflammation	DISB3X5A	moderate	Biomarker	[29]
Paraneoplastic syndrome	DISJUN66	moderate	Biomarker	[30]
Brachydactyly type E	DISM8YNM	Supportive	Autosomal dominant	[2]
Hereditary spastic paraplegia 2	DIS0TD1L	Disputed	Genetic Variation	[31]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[32]
T-cell leukaemia	DISJ6YIF	Disputed	Biomarker	[33]
Brachydactyly	DIS2533F	Limited	Genetic Variation	[34]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[35]
Prostate cancer	DISF190Y	Limited	Altered Expression	[24]
Pseudohypoparathyroidism type 1B	DIS9LDXL	Limited	Genetic Variation	[36]
Pulmonary disease	DIS6060I	Limited	Biomarker	[37]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	Parathyroid hormone-related protein (PTHLH) increases the abundance of [3H]cAMP.	[66]

31 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 Parathyroid hormone-related protein (PTHLH).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Parathyroid hormone-related protein (PTHLH).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Parathyroid hormone-related protein (PTHLH).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Parathyroid hormone-related protein (PTHLH).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Parathyroid hormone-related protein (PTHLH).	[43]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Parathyroid hormone-related protein (PTHLH).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Parathyroid hormone-related protein (PTHLH).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Parathyroid hormone-related protein (PTHLH).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Parathyroid hormone-related protein (PTHLH).	[47]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Parathyroid hormone-related protein (PTHLH).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Parathyroid hormone-related protein (PTHLH).	[49]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Parathyroid hormone-related protein (PTHLH).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Parathyroid hormone-related protein (PTHLH).	[51]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Parathyroid hormone-related protein (PTHLH).	[52]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Parathyroid hormone-related protein (PTHLH).	[51]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Parathyroid hormone-related protein (PTHLH).	[53]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Parathyroid hormone-related protein (PTHLH).	[54]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Parathyroid hormone-related protein (PTHLH).	[55]
Ceruletide	DM2WE5K	Approved	Ceruletide increases the expression of Parathyroid hormone-related protein (PTHLH).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Parathyroid hormone-related protein (PTHLH).	[48]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Parathyroid hormone-related protein (PTHLH).	[57]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Parathyroid hormone-related protein (PTHLH).	[58]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Parathyroid hormone-related protein (PTHLH).	[59]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Parathyroid hormone-related protein (PTHLH).	[60]
BETULINIC ACID	DMBUI2A	Phase 1	BETULINIC ACID decreases the expression of Parathyroid hormone-related protein (PTHLH).	[61]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Parathyroid hormone-related protein (PTHLH).	[62]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Parathyroid hormone-related protein (PTHLH).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Parathyroid hormone-related protein (PTHLH).	[63]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Parathyroid hormone-related protein (PTHLH).	[64]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Parathyroid hormone-related protein (PTHLH).	[65]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Parathyroid hormone-related protein (PTHLH).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the secretion of Parathyroid hormone-related protein (PTHLH).	[43]

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