Pirmitegravir is a potent, first-in-class allosteric integrase (ALLINI) inhibitor that targets the LEDGF/p75 binding site. Pirmitegravir displays picomolar IC50 in human PBMC and safety index against HIV-1 >24,000. Pirmitegravir has excellent antiviral and safety properties.

Physicochemical Properties

Molecular Formula	C27H31CLN4O3
Molecular Weight	495.013045549393
Exact Mass	494.208
CAS #	2245231-10-9
PubChem CID	142435949
Appearance	White to off-white solid powder
LogP	5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	740
Defined Atom Stereocenter Count	1
SMILES	CC1=C(N(C2=NC(=C(C(=C12)C3=CC=C(C=C3)Cl)[C@@H](C(=O)O)OC(C)(C)C)C)CC4=CN(N=C4)C)C
InChi Key	GNRDGAWRAIJOSU-DEOSSOPVSA-N
InChi Code	InChI=1S/C27H31ClN4O3/c1-15-17(3)32(14-18-12-29-31(7)13-18)25-21(15)23(19-8-10-20(28)11-9-19)22(16(2)30-25)24(26(33)34)35-27(4,5)6/h8-13,24H,14H2,1-7H3,(H,33,34)/t24-/m0/s1
Chemical Name	(2S)-2-[4-(4-chlorophenyl)-2,3,6-trimethyl-1-[(1-methylpyrazol-4-yl)methyl]pyrrolo[2,3-b]pyridin-5-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid
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)

Biological Activity

Targets	allosteric integrase (ALLINI)[1]
ln Vitro	At 1.4 nM IC50, pirmitegravir (Compound STP0404) suppresses dual tropic HIV-189.6 in CEMx174 cells[1]. Compound STP0404, pirmitegravir, is an extremely powerful ALLINI that suppresses HIV-1 strains resistant to Ral as well as wild type strains, with IC50 values ranging from picomolar to single-digit nanomolar[1]. When pristipegravir (Compound STP0404) is used at 10 μM (TC50 >10μM) in human PBMCs, it exhibits an IC50 of 0.41 nM against HIV-1NL4-3 without causing any discernible cytotoxicity[1].
ln Vivo	Compound STP0404, pirmitegravir, exhibits suitable PK characteristics for dosing once daily[1]. Compound STP0404, pirmitegravir, does not reduce bone marrow cell proliferation or induce micronuclei in rats when administered at doses of 500, 1000, and 2000 mg/kg/day, indicating that it is not genotoxic[1]. Evaluation of the pharmacokinetics (PK) profile in rats and dogs of pirmitegravir (Compound STP0404)[1]. 10 mg/kg (po), 5 mg/kg (iv), 2 mg/kg (po), 2 mg/kg (iv) T1/2 (hr) 4.56 3.83 6.90 6.11 AUC (hr.nM) 78074 42676 4683 9260 Cmax (nM) 21380 - 3983 - Ft (%) 92.8 - 50.6
Animal Protocol	Animal/Disease Models: SD rats and beagle dogs[1] Doses: 1, 2, 5, and 10 mg/kg Route of Administration: iv; po Experimental Results: The half-life ( T1/2) was 3–7 h, and oral bioavailability (Ft) was 50–93% in these two animal species. Systemic exposure, which was determined by area under the curve and maximum concentration of STP0404 in plasma (AUC and Cmax) , increased dose-dependently from 2 to 10 mg/kg.
References	[1]. A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. PLoS Pathog. 2021;17(7):e1009671.

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0202 mL	10.1008 mL	20.2016 mL
	5 mM	0.4040 mL	2.0202 mL	4.0403 mL
	10 mM	0.2020 mL	1.0101 mL	2.0202 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.