Details of the Drug

General Information of Drug (ID: DMOF2C6)

Drug Name

Ecallantide

Synonyms

FOV-2302; Retinal venous occlusion therapy, Fovea; Ecallantide (ophthalmic formulation/retinal disease); Ecallantide (ophthalmic formulation/retinal disease), Dyax/Fovea; DX-88 (ophthalmic formulation/retinal disease), Dyax/Fovea

Indication

Disease Entry	ICD 11	Status	REF
Retina venous occlusion	9B74.1	Approved	[1], [2]

Drug Type

Small molecular drug

Sequence

EAMHSFCAFKADDGPCRAAHPRWFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRD

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

7054

Topological Polar Surface Area (xlogp)

-27.9

Rotatable Bond Count (rotbonds)

133

Hydrogen Bond Donor Count (hbonddonor)

100

Hydrogen Bond Acceptor Count (hbondacc)

110

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 3017 +/- 402 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 586 +/- 106 mcg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2-3 h [3]
Clearance: The clearance of drug is 153 +/- 20 mL/min [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.0 +/- 0.5 hours [3]
Metabolism: The drug is not metabolised [5]
Vd: The volume of distribution (Vd) of drug is 26.4 +/- 7.8 L [4]

Chemical Identifiers

Formula: C305H442N88O91S8
IUPAC Name: (2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(1R,2aS,4S,5aS,8aS,11aR,13S,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,84S,87R,96S,99S)-22,42,45-tris(4-aminobutyl)-31-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-29a,72,78-tris(2-amino-2-oxoethyl)-14a,75-bis(3-amino-3-oxopropyl)-2a,23a,25,32a,35a,66-hexabenzyl-26a,99-bis[(2S)-butan-2-yl]-17a,41a,59a,69-tetrakis(3-carbamimidamidopropyl)-5a,8a,51,54,63,84-hexakis(2-carboxyethyl)-13,16-bis(carboxymethyl)-20a-[(1S)-1-hydroxyethyl]-60-(hydroxymethyl)-96-[(4-hydroxyphenyl)methyl]-50a-(1H-imidazol-5-ylmethyl)-38a-(1H-indol-3-ylmethyl)-19,28,53a,56a-tetramethyl-57-(2-methylpropyl)-39-(2-methylsulfanylethyl)-1a,3,4a,7a,9,10a,12,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,6a,8,9a,11,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.04,8.0144,148]nonahexacontahectane-36-carbonyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]butanedioic acid
Canonical SMILES: CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N4CCC[C@H]4C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N5CCC[C@H]5C(=O)N3)CC(=O)O)CC(=O)O)C)CCCCN)CC6=CC=CC=C6)C)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CO)NC(=O)[C@H](CC8=CN=CN8)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H]([C@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)CCSC)CCCCN)CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC2=O)CCC(=O)O)CC(=O)N)CCC(=O)N)CC(=O)N)CCCNC(=N)N)CC9=CC=CC=C9)CCC(=O)O)CO)CC(C)C)CCC(=O)O)CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CC1=CC=CC=C1)CCC(=O)O)CCC(=O)O)CCC(=O)N)CCCNC(=N)N)[C@H](C)O)CC1=CC=CC=C1)[C@@H](C)CC)CC(=O)N)CC1=CC=CC=C1)CC1=CC=CC=C1)CC1=CNC2=CC=CC=C21)CCCNC(=N)N)CC1=CN=CN1)C)C)CCCNC(=N)N)CC1=CC=C(C=C1)O
InChI: InChI=1S/C305H442N88O91S8/c1-16-152(5)241-295(478)377-195(124-168-80-82-172(398)83-81-168)252(435)334-137-227(404)333-138-228(405)345-214-143-487-491-147-218-291(474)351-179(73-47-107-327-301(315)316)255(438)341-154(7)245(428)339-155(8)249(432)379-210(127-171-136-326-150-338-171)299(482)393-113-53-79-221(393)294(477)361-181(75-49-109-329-303(319)320)260(443)372-203(125-169-134-332-175-69-40-39-68-173(169)175)277(460)370-198(119-163-58-29-20-30-59-163)274(457)369-199(120-164-60-31-21-32-61-164)275(458)375-207(130-226(314)403)284(467)389-242(153(6)17-2)296(479)378-202(123-167-66-37-24-38-67-167)283(466)390-243(159(12)396)297(480)362-182(76-50-110-330-304(321)322)258(441)353-186(86-94-223(311)400)267(450)383-217(290(473)359-188(89-98-234(414)415)263(446)354-189(90-99-235(416)417)265(448)368-201(282(465)388-241)122-166-64-35-23-36-65-166)146-490-489-145-216(384-268(451)191(92-101-237(420)421)355-262(445)187(88-97-233(412)413)357-271(454)194(116-151(3)4)366-285(468)212(141-394)381-266(449)190(91-100-236(418)419)358-273(456)197(118-162-56-27-19-28-57-162)367-259(442)180(74-48-108-328-302(317)318)349-280(463)206(129-225(313)402)374-264(447)185(85-93-222(310)399)356-279(462)205(128-224(312)401)344-229(406)139-335-251(434)184(352-288(214)471)87-96-232(410)411)289(472)350-178(72-43-46-106-308)256(439)347-177(71-42-45-105-307)257(440)360-193(103-115-486-15)270(453)385-219(292(475)391-244(160(13)397)298(481)363-183(77-51-111-331-305(323)324)261(444)380-211(300(483)484)133-240(426)427)148-492-488-144-215(386-276(459)200(121-165-62-33-22-34-63-165)371-286(469)213(142-395)382-278(461)204(126-170-135-325-149-337-170)373-269(452)192(102-114-485-14)346-246(429)156(9)340-250(433)174(309)84-95-231(408)409)287(470)343-158(11)247(430)364-196(117-161-54-25-18-26-55-161)272(455)348-176(70-41-44-104-306)254(437)342-157(10)248(431)365-209(132-239(424)425)281(464)376-208(131-238(422)423)253(436)336-140-230(407)392-112-52-78-220(392)293(476)387-218/h18-40,54-69,80-83,134-136,149-160,174,176-221,241-244,332,394-398H,16-17,41-53,70-79,84-133,137-148,306-309H2,1-15H3,(H2,310,399)(H2,311,400)(H2,312,401)(H2,313,402)(H2,314,403)(H,325,337)(H,326,338)(H,333,404)(H,334,435)(H,335,434)(H,336,436)(H,339,428)(H,340,433)(H,341,438)(H,342,437)(H,343,470)(H,344,406)(H,345,405)(H,346,429)(H,347,439)(H,348,455)(H,349,463)(H,350,472)(H,351,474)(H,352,471)(H,353,441)(H,354,446)(H,355,445)(H,356,462)(H,357,454)(H,358,456)(H,359,473)(H,360,440)(H,361,477)(H,362,480)(H,363,481)(H,364,430)(H,365,431)(H,366,468)(H,367,442)(H,368,448)(H,369,457)(H,370,460)(H,371,469)(H,372,443)(H,373,452)(H,374,447)(H,375,458)(H,376,464)(H,377,478)(H,378,479)(H,379,432)(H,380,444)(H,381,449)(H,382,461)(H,383,450)(H,384,451)(H,385,453)(H,386,459)(H,387,476)(H,388,465)(H,389,467)(H,390,466)(H,391,475)(H,408,409)(H,410,411)(H,412,413)(H,414,415)(H,416,417)(H,418,419)(H,420,421)(H,422,423)(H,424,425)(H,426,427)(H,483,484)(H4,315,316,327)(H4,317,318,328)(H4,319,320,329)(H4,321,322,330)(H4,323,324,331)/t152-,153-,154-,155-,156-,157-,158-,159-,160-,174-,176-,177-,178-,179-,180-,181-,182-,183-,184-,185-,186-,187-,188-,189-,190-,191-,192-,193-,194-,195-,196-,197-,198-,199-,200-,201-,202-,203-,204-,205-,206-,207-,208-,209-,210-,211-,212-,213-,214-,215-,216-,217-,218-,219-,220-,221-,241-,242-,243-,244-/m0/s1
InChIKey: VBGWSQKGUZHFPS-VGMMZINCSA-N

Cross-matching ID

PubChem CID: 44152182
CAS Number: 460738-38-9
DrugBank ID: DB05311
TTD ID: D0P5AE
ACDINA ID: D01026

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Kallikrein-related peptidase (KLK)	TT5L2VC	NOUNIPROTAC	Inhibitor	[6]
Plasma kallikrein (KLKB1)	TTMF8H9	KLKB1_HUMAN	Inhibitor	[6]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Potassium chloride	E00074	4873	Tonicity agent
Potassium phosphate monobasic	E00429	516951	Buffering agent
Disodium hydrogenorthophosphate	E00283	24203	Buffering agent; Complexing agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
--------------------

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ecallantide 10mg/ml injectable	10mg/ml	Injectable	Injection

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 6955).
2	ClinicalTrials.gov (NCT00969293) Study to Assess the Safety and Tolerability of a Single Administration of FOV2302 (Ecallantide) in Patients With Macular Edema Associated With Central Retinal Vein Occlusion. U.S. National Institutes of Health.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	Farkas H, Varga L: Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency. Clin Cosmet Investig Dermatol. 2011;4:61-8. doi: 10.2147/CCID.S10322. Epub 2011 May 31.
5	Kim ES: Lusutrombopag: First Global Approval. Drugs. 2016 Jan;76(1):155-8. doi: 10.1007/s40265-015-0525-4.
6	Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther. 2008 Aug;8(8):1187-99.
7	Characterization of a class of peptide boronates with neutral P1 side chains as highly selective inhibitors of thrombin. J Med Chem. 1995 Apr 28;38(9):1511-22.
8	A new broad spectrum inhibitor of esteroproteases, 4-(2-carboxyethyl) phenyl-trans-4-aminomethyl cyclohexane carboxylate hydrochloride (DV 1006). Tohoku J Exp Med. 1972 Mar;106(3):233-48.
9	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10	Serine protease inhibitors to treat inflammation: a patent review (2011-2016).Expert Opin Ther Pat. 2018 Feb;28(2):93-110.
11	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
12	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
13	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14	Clinical pipeline report, company report or official report of KalVista Pharmaceuticals.
15	Clinical pipeline report, company report or official report of Oxurion.
16	N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. J Med Chem. 2007 Oct 4;50(20):4928-38.
17	Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors. J Med Chem. 2008 Jun 12;51(11):3077-80.