(S)-2-amino-5-((S)-1-(carboxymethylamino)-3-(2,4-dinitrophenylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid

ID: ALA213947

Chembl Id: CHEMBL213947

PubChem CID: 25322935

Max Phase: Preclinical

Molecular Formula: C16H19N5O10S

Molecular Weight: 473.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  N[C@@H](CCC(=O)N[C@H](CSc1ccc([N+](=O)[O-])cc1[N+](=O)[O-])C(=O)NCC(=O)O)C(=O)O

Standard InChI:  InChI=1S/C16H19N5O10S/c17-9(16(26)27)2-4-13(22)19-10(15(25)18-6-14(23)24)7-32-12-3-1-8(20(28)29)5-11(12)21(30)31/h1,3,5,9-10H,2,4,6-7,17H2,(H,18,25)(H,19,22)(H,23,24)(H,26,27)/t9-,10+/m0/s1

Standard InChI Key:  FXEUKVKGTKDDIQ-VHSXEESVSA-N

Alternative Forms

1. Parent:

   

   ALA213947

   H-gGlu-D-Cys(Dnp)(Dnp)-Gly-OH

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 473.42

Molecular Weight (Monoisotopic): 473.0853

AlogP: -0.53

#Rotatable Bonds: 13

Polar Surface Area: 245.10

Molecular Species: ZWITTERION

HBA: 10

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 15

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 1.58

CX Basic pKa: 9.31

CX LogP: -3.30

CX LogD: -6.64

Aromatic Rings: 1

Heavy Atoms: 32

QED Weighted: 0.14

Np Likeness Score: -0.42

References

1. Shami PJ, Saavedra JE, Bonifant CL, Chu J, Udupi V, Malaviya S, Carr BI, Kar S, Wang M, Jia L, Ji X, Keefer LK..  (2006)  Antitumor activity of JS-K [O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and related O2-aryl diazeniumdiolates in vitro and in vivo.,  49  (14): [PMID:16821795] [10.1021/jm060022h]

2. Ishizuka H, Konno K, Naganuma H, Sasahara K, Kawahara Y, Niinuma K, Suzuki H, Sugiyama Y..  (1997)  Temocaprilat, a novel angiotensin-converting enzyme inhibitor, is excreted in bile via an ATP-dependent active transporter (cMOAT) that is deficient in Eisai hyperbilirubinemic mutant rats (EHBR).,  280  (1): [PMID:9067317]

3. Akita H, Suzuki H, Hirohashi T, Takikawa H, Sugiyama Y..  (2002)  Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3.,  19  (1): [PMID:11837698] [10.1023/a:1013699130991]

4. Kusuhara H, Han YH, Shimoda M, Kokue E, Suzuki H, Sugiyama Y..  (1998)  Reduced folate derivatives are endogenous substrates for cMOAT in rats.,  275  (1): [PMID:9756510] [10.1152/ajpgi.1998.275.4.g789]

5. Hirohashi T, Suzuki H, Sugiyama Y..  (1999)  Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3).,  274  (1): [PMID:10329726] [10.1074/jbc.274.21.15181]

6. Li L, Lee TK, Meier PJ, Ballatori N..  (1998)  Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter.,  273  (1): [PMID:9632674] [10.1074/jbc.273.26.16184]

7. Ito K, Suzuki H, Hirohashi T, Kume K, Shimizu T, Sugiyama Y..  (1998)  Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver.,  273  (1): [PMID:9430713] [10.1074/jbc.273.3.1684]

8. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD..  (2004)  Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11).,  67  (1): [PMID:15537867] [10.1124/mol.104.007138]

9. Heijn M, Hooijberg JH, Scheffer GL, Szabó G, Westerhoff HV, Lankelma J..  (1997)  Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport.,  1326  (1): [PMID:9188796] [10.1016/s0005-2736(97)00003-5]

10. Masuda M, I'izuka Y, Yamazaki M, Nishigaki R, Kato Y, Ni'inuma K, Suzuki H, Sugiyama Y..  (1997)  Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats.,  57  (1): [PMID:9270020]

11. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG..  (2002)  The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP.,  13  (1): [PMID:11856762] [10.1681/asn.v133595]

12. Hirohashi T, Suzuki H, Chu XY, Tamai I, Tsuji A, Sugiyama Y..  (2000)  Function and expression of multidrug resistance-associated protein family in human colon adenocarcinoma cells (Caco-2).,  292  (1): [PMID:10604957]

13. Niinuma K, Takenaka O, Horie T, Kobayashi K, Kato Y, Suzuki H, Sugiyama Y..  (1997)  Kinetic analysis of the primary active transport of conjugated metabolites across the bile canalicular membrane: comparative study of S-(2,4-dinitrophenyl)-glutathione and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole glucuronide.,  282  (1): [PMID:9262353]

14. Niinuma K, Kato Y, Suzuki H, Tyson CA, Weizer V, Dabbs JE, Froehlich R, Green CE, Sugiyama Y..  (1999)  Primary active transport of organic anions on bile canalicular membrane in humans.,  276  (1): [PMID:10330006] [10.1152/ajpgi.1999.276.5.g1153]

15. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD..  (2003)  Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).,  63  (1): [PMID:12527806] [10.1124/mol.63.2.351]

16. Ishizuka H, Konno K, Shiina T, Naganuma H, Nishimura K, Ito K, Suzuki H, Sugiyama Y..  (1999)  Species differences in the transport activity for organic anions across the bile canalicular membrane.,  290  (1): [PMID:10454510]

17. Jedlitschky G, Leier I, Buchholz U, Barnouin K, Kurz G, Keppler D..  (1996)  Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump.,  56  (1): [PMID:8640791]

18. Chen ZS, Kawabe T, Ono M, Aoki S, Sumizawa T, Furukawa T, Uchiumi T, Wada M, Kuwano M, Akiyama SI..  (1999)  Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter.,  56  (1): [PMID:10570049] [10.1124/mol.56.6.1219]

19. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y..  (2003)  ABCG2 transports sulfated conjugates of steroids and xenobiotics.,  278  (1): [PMID:12682043] [10.1074/jbc.m212399200]

20. Zeng H, Liu G, Rea PA, Kruh GD..  (2000)  Transport of amphipathic anions by human multidrug resistance protein 3.,  60  (1): [PMID:10987286]

21. Paulusma CC, van Geer MA, Evers R, Heijn M, Ottenhoff R, Borst P, Oude Elferink RP..  (1999)  Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione.,  338  (1): [PMID:10024515] [10.1042/0264-6021:3380393]

22. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD..  (2002)  Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6).,  62  (1): [PMID:12414644]

23. Jedlitschky G, Leier I, Böhme M, Buchholz U, Bar-Tana J, Keppler D..  (1994)  Hepatobiliary elimination of the peroxisome proliferator nafenopin by conjugation and subsequent ATP-dependent transport across the canalicular membrane.,  48  (1): [PMID:7945404] [10.1016/0006-2952(94)90147-3]

24. Madon J, Hagenbuch B, Landmann L, Meier PJ, Stieger B..  (2000)  Transport function and hepatocellular localization of mrp6 in rat liver.,  57  (1): [PMID:10692506] [10.1124/mol.57.3.634]

25. Ito K, Suzuki H, Sugiyama Y..  (2001)  Charged amino acids in the transmembrane domains are involved in the determination of the substrate specificity of rat Mrp2.,  59  (1): [PMID:11306690] [10.1124/mol.59.5.1077]

Source

Source(2):

• Scientific Literature
• TP-search Transporter Database