Details of the Drug

General Information of Drug (ID: DM0EZ9Q)

• Drug Name: Pramlintide
• Synonyms: Symlin; Triproamylin; Pramlintide [USAN]; Pramlintide acetate; Pramlintide acetate [USAN]; Pramlintide acetate hydrate; AC 0137

Indication

Disease Entry	ICD 11	Status	REF
Type-1/2 diabetes	5A10-5A11	Approved	[1]

• Affected Organisms: Humans and other mammals
• ATC Code:
  A10BX05: Pramlintide
  A10BX: Other blood glucose lowering drugs, excl. insulins
  A10B: BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
  A10: DRUGS USED IN DIABETES
  A: ALIMENTARY TRACT AND METABOLISM
• Drug Type: Small molecular drug
• Sequence:
  >Pramlintide
  KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 3949
  Logarithm of the Partition Coefficient (xlogp); -15.7
  Rotatable Bond Count (rotbonds); 110
  Hydrogen Bond Donor Count (hbonddonor); 56
  Hydrogen Bond Acceptor Count (hbondacc); 59
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Bioavailability: The bioavailability of drug is 30-40% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 15.3 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 48 minutes [3]
  Metabolism: The drug is metabolized via the kidneys []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00043 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.4% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.41 L/kg [3]
• Chemical Identifiers:
  Formula: C171H267N51O53S2
  IUPAC Name: (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S)-1-[[2-[(2S)-2-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2S,3R)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S,19R)-16-(2-amino-2-oxoethyl)-19-[[(2S)-2,6-diaminohexanoyl]amino]-7,13-bis[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]pentanediamide
  Canonical SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N)NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@@H]8CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N8)[C@@H](C)O)C)[C@@H](C)O)CC(=O)N)NC(=O)[C@H](CCCCN)N
  InChI: InChI=1S/C171H267N51O53S2/c1-21-81(12)130(163(268)207-110(56-78(6)7)169(274)222-53-33-42-118(222)170(275)221-52-32-41-117(221)160(265)219-135(89(20)230)167(272)206-109(66-125(180)238)151(256)212-128(79(8)9)161(266)186-68-126(239)192-111(70-223)154(259)203-107(64-123(178)236)152(257)218-134(88(19)229)166(271)195-98(136(181)241)57-92-43-45-94(231)46-44-92)214-159(264)116-40-31-51-220(116)127(240)69-187-141(246)101(58-90-34-24-22-25-35-90)199-148(253)105(62-121(176)234)201-149(254)106(63-122(177)235)202-155(260)112(71-224)209-156(261)113(72-225)208-146(251)103(60-93-67-184-75-188-93)205-162(267)129(80(10)11)213-150(255)100(55-77(4)5)198-145(250)102(59-91-36-26-23-27-37-91)200-147(252)104(61-120(175)233)196-137(242)82(13)189-144(249)99(54-76(2)3)197-142(247)96(39-30-50-185-171(182)183)193-143(248)97(47-48-119(174)232)194-165(270)132(86(17)227)215-138(243)83(14)190-157(262)114-73-276-277-74-115(210-140(245)95(173)38-28-29-49-172)158(263)204-108(65-124(179)237)153(258)217-131(85(16)226)164(269)191-84(15)139(244)216-133(87(18)228)168(273)211-114/h22-27,34-37,43-46,67,75-89,95-118,128-135,223-231H,21,28-33,38-42,47-66,68-74,172-173H2,1-20H3,(H2,174,232)(H2,175,233)(H2,176,234)(H2,177,235)(H2,178,236)(H2,179,237)(H2,180,238)(H2,181,241)(H,184,188)(H,186,266)(H,187,246)(H,189,249)(H,190,262)(H,191,269)(H,192,239)(H,193,248)(H,194,270)(H,195,271)(H,196,242)(H,197,247)(H,198,250)(H,199,253)(H,200,252)(H,201,254)(H,202,260)(H,203,259)(H,204,263)(H,205,267)(H,206,272)(H,207,268)(H,208,251)(H,209,261)(H,210,245)(H,211,273)(H,212,256)(H,213,255)(H,214,264)(H,215,243)(H,216,244)(H,217,258)(H,218,257)(H,219,265)(H4,182,183,185)/t81-,82-,83-,84-,85+,86+,87+,88+,89+,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,128-,129-,130-,131-,132-,133-,134-,135-/m0/s1
  InChIKey: TZIRZGBAFTZREM-MKAGXXMWSA-N
• Cross-matching ID:
  PubChem CID: 70691388
  ChEBI ID: CHEMBL135922
  CAS Number: 151126-32-8
  UNII: D3FM8FA78T
  DrugBank ID: DB01278
  TTD ID: D0C4AM
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucagon-like peptide 1 receptor (GLP1R)	TTVIMDE	GLP1R_HUMAN	Agonist	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Type-1/2 diabetes
• ICD Disease Classification: 5A10-5A11

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glucagon-like peptide 1 receptor (GLP1R)	DTT	GLP1R	1.25E-01	0.17	1.26

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Pramlintide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mepenzolate	DM8YU2F	Moderate	Altered absorption of Pramlintide due to GI dynamics variation caused by Mepenzolate.	Digestive system disease [DE2Z]	[6]
Solifenacin	DMG592Q	Moderate	Altered absorption of Pramlintide due to GI dynamics variation caused by Solifenacin.	Functional bladder disorder [GC50]	[6]
Belladonna	DM2RBWK	Moderate	Altered absorption of Pramlintide due to GI dynamics variation caused by Belladonna.	Infectious gastroenteritis/colitis [1A40]	[6]
Methylscopolamine	DM5VWOB	Moderate	Altered absorption of Pramlintide due to GI dynamics variation caused by Methylscopolamine.	Peptic ulcer [DA61]	[6]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7482).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [6] Product Information. Symlin (pramlintide). Amphastar Pharmaceuticals Inc, South El Monte, CA.