Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H21ClFN5O4 |
| Molecular Weight | 461.874 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1C[C@H](C)N2C(=C(O)C3=C2C(=NN(CC4=CC=C(F)C(Cl)=C4)C3=O)C(=O)NC)C1=O
InChI
InChIKey=JSRREMIKIHJGAA-JTQLQIEISA-N
InChI=1S/C21H21ClFN5O4/c1-4-26-8-10(2)28-16-14(18(29)17(28)21(26)32)20(31)27(25-15(16)19(30)24-3)9-11-5-6-13(23)12(22)7-11/h5-7,10,29H,4,8-9H2,1-3H3,(H,24,30)/t10-/m0/s1
| Molecular Formula | C21H21ClFN5O4 |
| Molecular Weight | 461.874 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created using several sources including: https://www.ncbi.nlm.nih.gov/pubmed/20799722|https://www.ncbi.nlm.nih.gov/pubmed/19906306
Curator's Comment: Description was created using several sources including: https://www.ncbi.nlm.nih.gov/pubmed/20799722|https://www.ncbi.nlm.nih.gov/pubmed/19906306
MK-2048, diketo acid derivative, is a second-generation integrase strand transfer inhibitor (INSTI) developed to retain activity against HIV containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). MK-2048 implements its inhibitory mechanism by modifying viral integrase-DNA interactions, the important step of the linear HIV-1 cDNA integration into the host genome. It binds to and inactivates the synaptic complex, an intermediate in the concerted integration pathway in vitro thereby preventing target DNA binding and concerted integration. MK-2048 is active against viruses resistant to RAL and EVG. MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H with a low IC50 value of 42 nM for inhibiting concerted integration. It inhibits R263K mutants slightly more effectively than G118R mutants. MK-2048 exposure leads to the selection of G118R as a possible novel resistance mutation.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
728 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30289435 |
30 mg 1 times / 4 weeks steady-state, vaginal dose: 30 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
MK-2048 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
277172 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30289435 |
30 mg 1 times / 4 weeks steady-state, vaginal dose: 30 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
MK-2048 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30289435 |
30 mg 1 times / 4 weeks steady-state, vaginal dose: 30 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
MK-2048 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes. | 2009 Nov 11 |
|
| Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. | 2010 Jul 5 |
|
| Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. | 2010 Sep |
|
| Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. | 2010 Sep 28 |
|
| Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes. | 2011 Nov |
Patents
Sample Use Guides
Intravaginal rings MK-2048A IVR (Low Dose) (91 mg of vicriviroc, 10 mg of MK-2048) or MK-2048A IVR (Original Dose) (182 mg of vicriviroc, 30 mg of MK-2048) inserted during the enrollment visit, and removed on Day 28
Route of Administration:
Vaginal
MK-2048 was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, to determine its relative potency and efficacy in different cellular systems of HIV infection. MK-2048 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells with the EC50 of 0.4, 0.9, 11.5 nM in macrophages, in PBMCs and T cells, respectively.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:30:40 GMT 2023
by
admin
on
Sat Dec 16 01:30:40 GMT 2023
|
| Record UNII |
LJ8U884TM5
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
DTXSID70236031
Created by
admin on Sat Dec 16 01:30:40 GMT 2023 , Edited by admin on Sat Dec 16 01:30:40 GMT 2023
|
PRIMARY | |||
|
MK-2048
Created by
admin on Sat Dec 16 01:30:40 GMT 2023 , Edited by admin on Sat Dec 16 01:30:40 GMT 2023
|
PRIMARY | |||
|
869901-69-9
Created by
admin on Sat Dec 16 01:30:40 GMT 2023 , Edited by admin on Sat Dec 16 01:30:40 GMT 2023
|
PRIMARY | |||
|
54698642
Created by
admin on Sat Dec 16 01:30:40 GMT 2023 , Edited by admin on Sat Dec 16 01:30:40 GMT 2023
|
PRIMARY | |||
|
LJ8U884TM5
Created by
admin on Sat Dec 16 01:30:40 GMT 2023 , Edited by admin on Sat Dec 16 01:30:40 GMT 2023
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
TARGET -> INHIBITOR |
Mutations (G118R and E138K) confer resistance to MK-2048
|
||
|
|
TARGET ORGANISM->INHIBITOR |
EC50
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
ACTIVE MOIETY |
|
