Details of the Drug

General Information of Drug (ID: DMGHQJ8)

Drug Name

N-(phosphonacetyl)-L-aspartate

Synonyms

Sparfosic acid; PALA; n-(phosphonacetyl)-l-aspartic acid; N-(Phosphonoacetyl)-L-aspartic acid; Sparfosic Acid [INN]; NSC-224131; UNII-78QVZ7RG8L; 51321-79-0; L-ASPARTIC ACID, N-(PHOSPHONOACETYL)-; N-Phosphonacetyl-L-aspartate; Phosphonacetyl-L-aspartic acid; Acidum sparfosicum [INN-Latin]; Acido sparfosico [INN-Spanish]; Acide sparfosique [INN-French]; N-(Phosphonoacetyl)-asparaginsaeure; N-(Phosphonacetyl)-L-Aspartate; 78QVZ7RG8L; (2S)-2-[(2-phosphonoacetyl)amino]butanedioic acid; Acido sparfosico; Acide sparfosique; Acidum; SPARFOSIC ACID

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1], [2], [3], [4], [5], [6], [7]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

252.1

Topological Polar Surface Area (xlogp)

-1.9

Rotatable Bond Count (rotbonds)

4

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C6H7NO8P-3
IUPAC Name: (2S)-2-[[2-[hydroxy(oxido)phosphoryl]acetyl]amino]butanedioate
Canonical SMILES: C([C@@H](C(=O)[O-])NC(=O)CP(=O)(O)[O-])C(=O)[O-]
InChI: InChI=1S/C6H10NO8P/c8-4(2-16(13,14)15)7-3(6(11)12)1-5(9)10/h3H,1-2H2,(H,7,8)(H,9,10)(H,11,12)(H2,13,14,15)/p-3/t3-/m0/s1
InChIKey: ZZKNRXZVGOYGJT-VKHMYHEASA-K

Cross-matching ID

PubChem CID: 46926274
TTD ID: D0L6CN

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aspartate carbamoyltransferase (CAD)	TT2YT1K	PYR1_HUMAN	Inhibitor	[1]
Carbonic anhydrase II (CA-II)	TTANPDJ	CAH2_HUMAN	Inhibitor	[7]
Carbonic anhydrase IV (CA-IV)	TTZHA0O	CAH4_HUMAN	Inhibitor	[7]
Pseudomonas Aspartate carbamoyltransferase (Pseudo pyrB)	TTDRBPW	PYRB_PSEPU	Inhibitor	[2], [3], [4], [5], [6]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Discovery agent

ICD Disease Classification

N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Carbonic anhydrase IV (CA-IV)	DTT	CA4	1.58E-77	-2.02	-1.77
Carbonic anhydrase II (CA-II)	DTT	CA2	7.95E-08	0.52	0.33

Molecular Expression Atlas (MEA)

MEA Detail

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References

1	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
2	Mechanism of resistance of variants of the Lewis lung carcinoma to N-(phosphonacetyl)-L-aspartic acid. Cancer Res. 1981 Mar;41(3):894-904.
3	Analogs of L-aspartic acid in chemotherapy for cancer. Cancer Treat Rep. 1979 Jun;63(6):1095-108.
4	Aspartate carbamoyltransferase activity, drug concentrations, and pyrimidine nucleotides in tissue from patients treated with N-(phosphonacetyl)-L-aspartate. Biochem Pharmacol. 1982 Oct 15;31(20):3317-21.
5	Long-term association of N-(phosphonacetyl)-L-aspartate with bone. Cancer Res. 1981 Jan;41(1):150-6.
6	Penetration of N-(phosphonacetyl)-L-aspartate into human central nervous system and intracerebral tumor. Cancer Res. 1980 Sep;40(9):3163-6.
7	Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with organic phosphates and phosphonates. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1683-6.
8	Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.
9	Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases. J Med Chem. 2010 Apr 8;53(7):2913-26.
10	Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
11	Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats. Clin Sci (Lond). 2000 Apr;98(4):481-8.
12	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
13	Selective effect of thiazides on the human osteoblast-like cell line MG-63. Kidney Int. 1996 Nov;50(5):1476-82.
14	Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50.
15	Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4.
16	Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
17	Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.
18	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
19	Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
20	Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-r... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6.
21	Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. Bioorg Med Chem Lett. 2005 Feb 1;15(3):573-8.
22	Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mamm... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5.