| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
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| Other Sizes |
| Targets |
HIV-1 reverse transcriptase (nonnucleoside reverse transcriptase inhibitor, NNRTI) and HIV-1 entry inhibitor (dual mechanism of action)[1]
HIV-1 EC50 of 0.2 nM[1] HIV-2 EC50 of 100 nM[1] IC90 of 146 ng/mL[1] |
|---|---|
| ln Vitro |
IQP-0528 has nanomolar activity against HIV-1 (EC50 0.2 nM) and HIV-2 (EC50 100 nM).[1]
IQP-0528 demonstrates dual mechanism of action: prevents HIV-1 entry (EC50 of 12 nM) and inhibits reverse transcription.[1] IQP-0528 has poor aqueous solubility and a calculated LogP of 4.1.[1] IQP-0528 formulated in a 0.1% w/w vaginal film showed complete in vitro release after 30 minutes.[1] IQP-0528 in a 3.0% HEC gel containing 0.25% IQP-0528 was found to be safe and effective against HIV-1 in vitro and ex vivo.[1] A combination 2.5% TFV/1% IQP-0528 dual compartment gel was effective against HIV-1 in colorectal and ectocervical tissue ex vivo, with an EC50 between that of IQP-0528 and TFV.[1] |
| ln Vivo |
In pigtailed macaques, intravaginal rings (IVRs) loaded with IQP-0528 (15.6% wt in Tecoflex 85A) delivered drug to vaginal fluid at levels well in excess of the IC90 (146 ng/mL) over 28 days, with concentrations ranging from 1.4×10² to 3.2×10⁵ ng/mL in proximal vaginal fluid.[1]
No statistically significant difference was observed in vaginal fluid or tissue drug levels between IVRs with full, half, or quarter drug-loaded segments in vivo.[1] Vaginal tissue levels of IQP-0528 were highly variable but consistently above the IC90, with levels ranging from 54 to 2.0×10⁵ ng/g tissue across different vaginal sites and time points.[1] No drug was detected in plasma samples, indicating minimal systemic exposure.[1] Following IVR removal, vaginal fluid drug levels dropped significantly within 2 days, indicating short duration of residual protection.[1] |
| Cell Assay |
Proliferation assay (immunocytochemistry): LM7 cells were seeded on polylysine-coated coverslips in 24-well plates. After 24 hours, cells were treated with Fenobam (300 µM) or other drugs for 72 hours. Cells were fixed, permeabilized, and stained with anti-Ki-67 antibody and DAPI. Ki-67-positive and DAPI-positive cells were counted using fluorescence microscopy.[2]
TUNEL assay (apoptosis): LM7 cells were treated with Fenobam (300 µM) for 72 hours. Cells were fixed, permeabilized, and incubated with TUNEL reagent containing TMR red-labeled nucleotides. TUNEL-positive and DAPI-positive cells were counted using fluorescence microscopy.[2] Western blot: Whole cell extracts from LM7 cells were analyzed by SDS-PAGE and immunoblotting using antibodies against mGluR5 to confirm receptor expression.[2] |
| Animal Protocol |
Pigtailed macaque pharmacokinetic study:** Six sexually mature female pigtailed macaques were enrolled in a crossover study. Each animal received a matrix IVR containing IQP-0528 (15.6% wt in Tecoflex 85A) with varying lengths of drug-loaded segment (full, half, or quarter of the ring) inserted into the upper posterior vagina near the ectocervix on day 0 and removed on day 28. There was a two-week washout period between each crossover. Vaginal fluid was sampled using surgical sponges at days 0, 3, 7, 14, 21, 28, and 30 (2 days post-removal). Vaginal biopsies were collected at days 14 and 28 from proximal, medial, and distal sites. Blood plasma was also collected. Animals were anesthetized with ketamine (10 mg/kg IM) supplemented with Telazol (2–6 mg/kg) as needed.[1]
**IVR preparation:** Matrix IVRs were made by injection molding of drug-loaded Tecoflex EG85A pellets. Drug-loaded segments were butt-welded to blank segments to create full, half, and quarter rings with outer diameter of 25 mm and segment diameter of 5 mm.[1] Pigtailed macaque pharmacokinetic study: Six sexually mature female pigtailed macaques were enrolled in a crossover study. Each animal received a matrix IVR containing IQP-0528 (15.6% wt in Tecoflex 85A) with varying lengths of drug-loaded segment (full, half, or quarter of the ring) inserted into the upper posterior vagina near the ectocervix on day 0 and removed on day 28. There was a two-week washout period between each crossover. Vaginal fluid was sampled using surgical sponges at days 0, 3, 7, 14, 21, 28, and 30 (2 days post-removal). Vaginal biopsies were collected at days 14 and 28 from proximal, medial, and distal sites. Blood plasma was also collected. Animals were anesthetized with ketamine (10 mg/kg IM) supplemented with Telazol (2–6 mg/kg) as needed.[1] IVR preparation: Matrix IVRs were made by injection molding of drug-loaded Tecoflex EG85A pellets. Drug-loaded segments were butt-welded to blank segments to create full, half, and quarter rings with outer diameter of 25 mm and segment diameter of 5 mm.[1] |
| ADME/Pharmacokinetics |
IQP-0528 released from IVRs in vivo showed an average daily release of approximately 0.02–0.03 mg/day, which is more than an order of magnitude lower than in vitro release rates under sink conditions.[1]
Vaginal fluid concentrations of IQP-0528 were highly variable but remained above the IC90 (146 ng/mL) throughout the 28-day study period.[1] No drug was detected in plasma samples (LLOQ 5 ng/mL), indicating negligible systemic absorption.[1] Drug levels in vaginal tissue were also highly variable but sustained above protective levels.[1] In vivo release was not proportional to ring loading or surface area, likely due to poor solubility and saturation of cervicovaginal fluid.[1] |
| References | |
| Additional Infomation |
IQP-0528 is currently being studied in the clinical trial NCT03082690 (ImQuest (IQP) DuoGel Phase 1 Pharmacokinetic Study).
IQP-0528 is a dual-action NNRTI with entry inhibition activity, making it a candidate for single-drug combination therapy.[1] It has poor aqueous solubility, which influences its release kinetics from intravaginal rings in vivo.[1] In vitro release under sink conditions (in acetate buffer with solubilizer) showed dose-proportional release, but this did not translate to in vivo release due to saturation of vaginal fluid and slow clearance.[1] Even low loadings of IQP-0528 in IVRs can achieve vaginal fluid levels far above the IC90, suggesting potential for low-dose formulations in combination rings.[1] The study highlights that in vitro release may not accurately predict in vivo release for poorly soluble drugs delivered via IVRs.[1] |
| Exact Mass |
340.179
|
|---|---|
| CAS # |
301297-45-0
|
| PubChem CID |
483499
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.33
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
25
|
| Complexity |
608
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(=O)N(CC2CC2)C(C(=O)C2=CC(C)=CC(C)=C2)=C(C(C)C)C(=O)N1
|
| InChi Key |
UCOAKFIVSAVHLC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H24N2O3/c1-11(2)16-17(18(23)15-8-12(3)7-13(4)9-15)22(10-14-5-6-14)20(25)21-19(16)24/h7-9,11,14H,5-6,10H2,1-4H3,(H,21,24,25)
|
| Chemical Name |
1-(cyclopropylmethyl)-6-(3,5-dimethylbenzoyl)-5-propan-2-ylpyrimidine-2,4-dione
|
| Synonyms |
IQP-0528 IQP0528 IQP 0528
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03082690 | COMPLETED | Drug: DuoGel | HIV Prevention | Johns Hopkins University | 2017-11-01 | Phase 1 |
|
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