Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQKU2F5)

DOT Name	Chorionic somatomammotropin hormone-like 1 (CSHL1)
Synonyms	Chorionic somatomammotropin-like; Lactogen-like
Gene Name	CSHL1
Related Disease	Advanced cancer ( ) Breast neoplasm ( ) Glioblastoma multiforme ( ) Hereditary angioedema ( ) Hypogonadotropic hypogonadism ( ) Hypogonadotropic hypogonadism 23 with or without anosmia ( ) Hypopituitarism ( ) Kallmann syndrome ( ) leukaemia ( ) Leukemia ( ) Neoplasm ( ) Panhypopituitarism ( ) Pituitary dwarfism ( ) Precancerous condition ( ) Skin cancer ( ) Squamous cell carcinoma ( ) Von willebrand disease ( ) Breast cancer ( ) Breast carcinoma ( ) Isolated growth hormone deficiency type II ( ) Kaposi sarcoma ( ) Cutaneous squamous cell carcinoma ( ) Non-insulin dependent diabetes ( )
UniProt ID	CSHL_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00103
Sequence	MAAGSRTSLLLAFALLCLPWLQEAGAVQTVPLSRLFKEAMLQAHRAHQLAIDTYQEFISS WGMEAYITKEQKYSFLHDSQTSFCFSDSIPTSSNMEETQQKSNLELLHISLLLIESRLEP VRFLRSTFTNNLVYDTSDSDDYHLLKDLEEGIQMLMGRLEDGSHLTGQTLKQTYSKFDTN SHNHDALLKNYGLLHCFRKDMDKVETFLRMVQCRSVEGSCGF
Function	May be a novel gestational hormone required to compensate for absence of other members of the GH/CS cluster during gestation.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hereditary angioedema	DIS8X53J	Strong	Genetic Variation	[4]
Hypogonadotropic hypogonadism	DIS8JSKR	Strong	Biomarker	[5]
Hypogonadotropic hypogonadism 23 with or without anosmia	DISYNM6Y	Strong	Biomarker	[5]
Hypopituitarism	DIS1QT3G	Strong	Biomarker	[5]
Kallmann syndrome	DISO3HDG	Strong	Biomarker	[5]
leukaemia	DISS7D1V	Strong	Altered Expression	[6]
Leukemia	DISNAKFL	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Panhypopituitarism	DISAKJ4T	Strong	Biomarker	[5]
Pituitary dwarfism	DISI019B	Strong	Biomarker	[5]
Precancerous condition	DISV06FL	Strong	Biomarker	[8]
Skin cancer	DISTM18U	Strong	Altered Expression	[7]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[9]
Von willebrand disease	DIS3TZCH	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	moderate	Biomarker	[11]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[11]
Isolated growth hormone deficiency type II	DISH3EO5	moderate	Biomarker	[5]
Kaposi sarcoma	DISC1H1Z	Disputed	Biomarker	[12]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[13]
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⏷ Show the Full List of 23 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Chorionic somatomammotropin hormone-like 1 (CSHL1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Chorionic somatomammotropin hormone-like 1 (CSHL1).	[16]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Chorionic somatomammotropin hormone-like 1 (CSHL1).	[15]
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References

1	CSL controls telomere maintenance and genome stability in human dermal fibroblasts.Nat Commun. 2019 Aug 29;10(1):3884. doi: 10.1038/s41467-019-11785-7.
2	NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells.Cancer Res. 2008 Mar 15;68(6):1881-8. doi: 10.1158/0008-5472.CAN-07-1597.
3	Deltex-1 activates mitotic signaling and proliferation and increases the clonogenic and invasive potential of U373 and LN18 glioblastoma cells and correlates with patient survival.PLoS One. 2013;8(2):e57793. doi: 10.1371/journal.pone.0057793. Epub 2013 Feb 25.
4	Population pharmacokinetics of subcutaneous C1-inhibitor for prevention of attacks in patients with hereditary angioedema.Clin Exp Allergy. 2018 Oct;48(10):1325-1332. doi: 10.1111/cea.13220. Epub 2018 Aug 26.
5	A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.Endocrinology. 2004 May;145(5):2531-41. doi: 10.1210/en.2003-1125. Epub 2004 Jan 15.
6	CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia.J Exp Med. 2009 Apr 13;206(4):779-91. doi: 10.1084/jem.20081922. Epub 2009 Apr 6.
7	Autophagy Controls CSL/RBPJ Stability through a p62/SQSTM1-Dependent Mechanism.Cell Rep. 2018 Sep 18;24(12):3108-3114.e4. doi: 10.1016/j.celrep.2018.08.043.
8	Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.Nat Cell Biol. 2015 Sep;17(9):1193-204. doi: 10.1038/ncb3228. Epub 2015 Aug 24.
9	Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B.J Clin Invest. 2018 Jun 1;128(6):2581-2599. doi: 10.1172/JCI96915. Epub 2018 May 14.
10	Pharmacokinetics, efficacy, and safety of a plasma-derived VWF/FVIII concentrate (VONCENTO) for on-demand and prophylactic treatment in patients with von Willebrand disease (SWIFT-VWD study).Blood Coagul Fibrinolysis. 2017 Mar;28(2):152-162. doi: 10.1097/MBC.0000000000000568.
11	Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells.Stem Cell Reports. 2016 May 10;6(5):643-651. doi: 10.1016/j.stemcr.2016.03.004. Epub 2016 Apr 7.
12	A herpesvirus transactivator and cellular POU proteins extensively regulate DNA binding of the host Notch signaling protein RBP-J to the virus genome.J Biol Chem. 2019 Aug 30;294(35):13073-13092. doi: 10.1074/jbc.RA118.007331. Epub 2019 Jul 15.
13	Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation.Metabolism. 2002 Jan;51(1):1-4. doi: 10.1053/meta.2002.28973.
14	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
15	Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
16	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.