ID: ALA176049

Max Phase: Preclinical

Molecular Formula: C21H17ClN2O3

Molecular Weight: 344.37

Molecule Type: Small molecule

Representations

Synonyms (1): Rhodamine 123
Synonyms from Alternative Forms(1):

Canonical SMILES:  COC(=O)c1ccccc1-c1c2ccc(=N)cc-2oc2cc(N)ccc12.Cl

Standard InChI:  InChI=1S/C21H16N2O3.ClH/c1-25-21(24)15-5-3-2-4-14(15)20-16-8-6-12(22)10-18(16)26-19-11-13(23)7-9-17(19)20;/h2-11,22H,23H2,1H3;1H

Standard InChI Key:  MYFATKRONKHHQL-UHFFFAOYSA-N

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

Properties

Molecular Weight: 344.37

Molecular Weight (Monoisotopic): 344.1161

AlogP: 4.05

#Rotatable Bonds: 2

Polar Surface Area: 89.31

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 7.70

CX LogP: 2.85

CX LogD: 2.37

Aromatic Rings: 2

Heavy Atoms: 26

QED Weighted: 0.33

Np Likeness Score: 0.30

References

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2. Müller H, Klinkhammer W, Globisch C, Kassack MU, Pajeva IK, Wiese M..  (2007)  New functional assay of P-glycoprotein activity using Hoechst 33342.,  15  (23): [PMID:17890094] [10.1016/j.bmc.2007.07.024]

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4. Staerk D, Lykkeberg AK, Christensen J, Budnik BA, Abe F, Jaroszewski JW..  (2002)  In vitro cytotoxic activity of phenanthroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells.,  65  (9): [PMID:12350151] [10.1021/np0106384]

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6. Puri N, Prakash O, Manoharlal R, Sharma M, Ghosh I, Prasad R..  (2010)  Analysis of physico-chemical properties of substrates of ABC and MFS multidrug transporters of pathogenic Candida albicans.,  45  (11): [PMID:20739103] [10.1016/j.ejmech.2010.07.050]

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9. Kim AE, Dintaman JM, Waddell DS, Silverman JA..  (1998)  Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein.,  286  (1): [PMID:9732409]

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12. Tang F, Ouyang H, Yang JZ, Borchardt RT..  (2004)  Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MDCK-MDR1 cell monolayers.,  93  (1): [PMID:15067695] [10.1002/jps.20046]

13. de Lange EC, de Bock G, Schinkel AH, de Boer AG, Breimer DD..  (1998)  BBB transport and P-glycoprotein functionality using MDR1A (-/-) and wild-type mice. Total brain versus microdialysis concentration profiles of rhodamine-123.,  15  (1): [PMID:9833984] [10.1023/a:1011988024295]

14. Santoni-Rugiu E, Silverman JA..  (1997)  Functional characterization of the rat mdr1b encoded P-glycoprotein: not all inducing agents are substrates.,  18  (1): [PMID:9395229] [10.1093/carcin/18.11.2255]

15. Wang EJ, Casciano CN, Clement RP, Johnson WW..  (2003)  Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites.,  20  (1): [PMID:12739759] [10.1023/a:1023278211849]

16. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD..  (2000)  Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.,  57  (1): [PMID:10617675]

17. Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW..  (2003)  Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis.,  278  (1): [PMID:12668685] [10.1074/jbc.m301358200]

18. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD..  (2003)  Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis.,  64  (1): [PMID:14645676] [10.1124/mol.64.6.1452]

19. Ozvegy C, Litman T, Szakács G, Nagy Z, Bates S, Váradi A, Sarkadi B..  (2001)  Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells.,  285  (1): [PMID:11437380] [10.1006/bbrc.2001.5130]

20. Byeon SR, Kim HV, Jeon M, Ahn YG, Kim MS, Kong JY, Kim HY, Kim YS, Kim DJ..  (2013)  Therapeutic and pharmacokinetic characterizations of an anti-amyloidogenic bis-styrylbenzene derivative for Alzheimer's disease treatment.,  23  (11): [PMID:23601707] [10.1016/j.bmcl.2013.02.104]

21. Farrell TL, Poquet L, Dew TP, Barber S, Williamson G..  (2012)  Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.,  40  (2): [PMID:22096083] [10.1124/dmd.111.041665]

22. Fraunhofer Institute for Translational Medicine and Pharmacology - Discovery Research – ScreeningPort.  (2021)  ECBD screening data for assay EOS300033,  [10.6019/EOS300033]

Source

Source(3):

• Scientific Literature
• TP-search Transporter Database
• EU-OPENSCREEN dataset