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Details

Stereochemistry ABSOLUTE
Molecular Formula C33H44N4O6S
Molecular Weight 624.793
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PPL-100

SMILES

CC(C)CN([C@@]([H])(CCCCN=C([C@]([H])(C(c1ccccc1)c2ccccc2)N=C(O)OC)O)CO)S(=O)(=O)c3ccc(cc3)N

InChI

InChIKey=QAHLFXYLXBBCPS-IZEXYCQBSA-N
InChI=1S/C33H44N4O6S/c1-24(2)22-37(44(41,42)29-19-17-27(34)18-20-29)28(23-38)16-10-11-21-35-32(39)31(36-33(40)43-3)30(25-12-6-4-7-13-25)26-14-8-5-9-15-26/h4-9,12-15,17-20,24,28,30-31,38H,10-11,16,21-23,34H2,1-3H3,(H,35,39)(H,36,40)/t28-,31-/m0/s1

HIDE SMILES / InChI

Molecular Formula C33H44N4O6S
Molecular Weight 624.793
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

MX-100 (also known as PL-100) is a benzenesulfonamide derivative patented by Pharmacor Inc as HIV aspartyl protease inhibitor. MX-100 retained excellent antiviral activity against almost all of these protease inhibitor-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC50 for MX-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs. Preclinical studies showed that MX-100 possessed suboptimal solubility and pharmacokinetic, (PK) properties, possibly hindering further development. MX-100 successfully completed preclinical and clinical development (phase I in healthy volunteers) and have been licensed to Merck in 2006

Approval Year

PubMed

PubMed

TitleDatePubMed
Epsilon substituted lysinol derivatives as HIV-1 protease inhibitors.
2010 Jul 15
Assessment of the susceptibility of mutant HIV-1 to antiviral agents.
2010 May
In vitro and structural evaluation of PL-100 as a potential second-generation HIV-1 protease inhibitor.
2013 Jan
Patents

Sample Use Guides

300- 2400 mg
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:15:44 UTC 2021
Edited
by admin
on Sat Jun 26 05:15:44 UTC 2021
Record UNII
JRI5GOF0K0
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PPL-100
Common Name English
PPL 100
Code English
MK-8122
Code English
CARBAMIC ACID, ((1S)-1-((((5S)-5-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-6-HYDROXYHEXYL)AMINO)CARBONYL)-2,2-DIPHENYLETHYL)-, METHYL ESTER
Systematic Name English
METHYL N-((1S)-1-(((5S)-5-((4-AMINOPHENYL)SULFONYL-ISOBUTYL-AMINO)-6-HYDROXY-HEXYL)CARBAMOYL)-2,2-DIPHENYL-ETHYL)CARBAMATE
Systematic Name English
PL 100 (PHARMACEUTICAL)
Code English
MX-100
Code English
TMB-607
Code English
PL-100
Common Name English
Code System Code Type Description
FDA UNII
JRI5GOF0K0
Created by admin on Sat Jun 26 05:15:44 UTC 2021 , Edited by admin on Sat Jun 26 05:15:44 UTC 2021
PRIMARY
DRUG BANK
DB05961
Created by admin on Sat Jun 26 05:15:44 UTC 2021 , Edited by admin on Sat Jun 26 05:15:44 UTC 2021
PRIMARY
PUBCHEM
513956
Created by admin on Sat Jun 26 05:15:44 UTC 2021 , Edited by admin on Sat Jun 26 05:15:44 UTC 2021
PRIMARY
CAS
612547-11-2
Created by admin on Sat Jun 26 05:15:44 UTC 2021 , Edited by admin on Sat Jun 26 05:15:44 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
Related Record Type Details
ACTIVE MOIETY
In the present study, we compared the antiviral activity of PL-100 against HIV-1 subtype B with that of darunavir. We used tissue culture experiments to evaluate the in vitro development of resistance to PL-100 and tested the antiviral activity of several clinically approved PIs against PL-100-selected resistant variants. Structural modelling was also used to compare the binding of PL-100 and darunavir to the HIV-1 protease (PR) enzyme.PL-100-resistant variants that emerged within 8-48 weeks showed low- to high-level resistance (3.5- to 21.6-fold) to PL-100, but commonly retained susceptibility to darunavir, which, in contrast, did not select for resistance mutations over a period of 40 weeks. Hydrogen-bonding contacts and the di-THF group in darunavir, as well as the hydrophobic nature of PL-100, contribute to PI binding and a high genetic barrier for resistance. Redesigning the structure of PL-100 to include a di-THF group might improve it.
ACTIVE MOIETY
A selection for resistance against PL-100 in cord blood mononuclear cells was performed, using the laboratory-adapted IIIb strain of HIV-1, and it was shown that resistance appears to develop slower against this compound than against amprenavir, which was studied as a control. Four mutations in protease (PR) were selected after 25 weeks: two flap mutations (K45R and M46I) and two novel active site mutations (T80I and P81S).
ACTIVE MOIETY
Class: Aniline compound, Antiretroviral, Benzhydryl compound, Carbamate, Phosphoric acid ester, Small molecule, Sulfonamide; Mechanism of Action: HIV protease inhibitor; Highest Development Phase: Preclinical for HIV infection; Most Recent Events: 20 May 2016 PPl 100 (SC, IM) is still in preclinical development for HIV infections in Taiwan, 09 Jul 2013 No development reported - Phase-I for HIV infections in Canada (PO)