Drug Information

Drug (ID: DG01158) and It's Reported Resistant Information

• Name: Saralasin
• Synonyms: Saralasin; 34273-10-4; (Sar1,Val5,Ala8)-Angiotensin II; Sar-Arg-Val-Tyr-Val-His-Pro-Ala; UNII-H2AFV2HE66; CHEMBL938; H2AFV2HE66; (2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoic acid; Saralasina; Saralasine; Saralasinum; Saralasinum [INN-Latin]; Saralasin [INN:BAN]; Saralasine [INN-French]; Saralasina [INN-Spanish]; NCGC00166135-01; Angiotensin II, 1-(N-methylglycine)-5-L-valine-8-L-alanine-; SCHEMBL23; DSSTox_CID_26549; DSSTox_RID_81710; DSSTox_GSID_46549; 1-Sar-8-Ala-angiotensin II; DTXSID2046549; CHEBI:135894; (1-(N-Methylglycin) 5-L-valin, 8-L-alanin)angiotensin II; Tox21_112332; BDBM50009338; BDBM50229504; AKOS024456428; Sar-Arg-Val-Tyr-Val-His-Pro-Ala-OH; ZINC169289386; DB06763; NCGC00167316-01; N-(1-(N-(N-(N-(N-(N2-(N-methylglycly)-L-arginyl)-L-valyl)-L-tyrosyl)-L-valyl)-L-histidyl)-L-prolyl)-L-alanine; CAS-34273-10-4; Sar-Arg-Val-Tyr-Val-His-Pro-Ala (sarlasin); [Sar1-Arg2-Val3-Tyr4-Val5-His6-Pro7-Ala8]; Q410298; (S)-2-((S)-1-((6S,9S,12S,15S,18S)-18-((1H-imidazol-4-yl)methyl)-6-(3-guanidinopropyl)-12-(4-hydroxybenzyl)-9,15-diisopropyl-4,7,10,13,16-pentaoxo-2,5,8,11,14,17-hexaazanonadecane)pyrrolidine-2-carboxamido)propanoic acid; (S)-2-((S)-1-((S)-2-((S)-2-((S)-2-((S)-2-((S)-5-(diaminomethyleneamino)-2-(2-(methylamino)acetamido)pentanamido)-3-methylbutanamido)-3-(4-hydroxyphenyl)propanamido)-3-methylbutanamido)-3-(1H-imidazol-5-yl)propanoyl)pyrrolidine-5-carboxamido)propanoic acid
• Indication:
  In total 1 Indication(s)
  Hypertension [ICD-11: BA00]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Hypertension [ICD-11: BA00]; [1]
• Target: Angiotensin II receptor type-1 (AGTR1); AGTR1_HUMAN; [1]
• Target: Angiotensin II receptor type-2 (AGTR2); AGTR2_HUMAN; [1]
• Formula: C42H65N13O10
• IsoSMILES: C[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC
• InChI: 1S/C42H65N13O10/c1-22(2)33(53-35(58)28(50-32(57)20-45-6)9-7-15-47-42(43)44)38(61)51-29(17-25-11-13-27(56)14-12-25)36(59)54-34(23(3)4)39(62)52-30(18-26-19-46-21-48-26)40(63)55-16-8-10-31(55)37(60)49-24(5)41(64)65/h11-14,19,21-24,28-31,33-34,45,56H,7-10,15-18,20H2,1-6H3,(H,46,48)(H,49,60)(H,50,57)(H,51,61)(H,52,62)(H,53,58)(H,54,59)(H,64,65)(H4,43,44,47)/t24-,28-,29-,30-,31-,33-,34-/m0/s1
• InChIKey: PFGWGEPQIUAZME-NXSMLHPHSA-N
• PubChem CID: 6324663
• ChEBI ID: CHEBI:135894
• TTD Drug ID: D0K0AT

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-11: Circulatory system diseases

Hypertension [ICD-11: BA00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Natriuretic peptides A (ANF) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Hypertension [ICD-11: BA00.Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Two-kidney,one-clip hypertensive rat; Rattus norvegicus
• Experiment for Drug Resistance: Pressure measurement
• Mechanism Description: Saralasin-resistant rats exhibited a decreased number of vascular ANF binding sites in both mesenteric arteries and aorta. We conclude that through modulation of its glomerular and vascular receptors, ANF may contribute to the differential sodium handling of saralasin-sensitive and -resistant 2K1C hypertensive rats and to the reduced vascular responsiveness to ANF observed in the saralasin-resistant hypertensive rats.

References

• Ref 1: Glomerular and vascular atrial natriuretic factor receptors in saralasin-sensitive and -resistant two-kidney, one-clip hypertensive rats .Circ Res. 1988 Sep;63(3):563-71. doi: 10.1161/01.res.63.3.563. 10.1161/01.res.63.3.563