Rac-Efavirenz targets HIV-1 reverse transcriptase, the same target as the active (S)-enantiomer, Efavirenz. As a non-nucleoside reverse transcriptase inhibitor (NNRTI), it binds to an allosteric site on the enzyme and inhibits its polymerase activity. The racemic mixture contains both the active and inactive enantiomers.

Specific in vitro activity data for Rac-Efavirenz are not detailed in the available literature, as it is primarily used as a reference standard. The active (S)-enantiomer, Efavirenz, is well-characterized and shows potent inhibition of HIV-1 reverse transcriptase. The racemic mixture would have reduced activity compared to the pure active enantiomer.

Specific in vivo activity data for Rac-Efavirenz are not available in the literature, as it is not used as a therapeutic agent. It is a reference standard for research and analytical purposes, not for in vivo studies.

In vitro enzyme assays for Rac-Efavirenz would measure its inhibition of HIV-1 reverse transcriptase, similar to the active enantiomer. A typical assay uses recombinant HIV-1 RT and a template-primer with radiolabeled nucleotides. The compound is incubated with the enzyme, and the inhibition of nucleotide incorporation is measured to determine the IC50.

In vitro cell-based assays for Rac-Efavirenz would involve treating HIV-1-susceptible cell lines with the compound and measuring viral replication, similar to the active enantiomer. However, as a reference standard, it is not typically used in cell-based assays.

In vivo animal models are not applicable to Rac-Efavirenz, as it is a reference standard and not a therapeutic agent. It is not evaluated in animal models for efficacy.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Efavirenz is excreted into breast milk, and trace amounts can be detected in the serum of some infants. Treatment with efavirenz in HIV-positive mothers does not appear to affect the growth and development of their HIV-negative breastfed infants. Achieving and maintaining viral suppression through antiretroviral therapy can reduce the risk of breast milk transmission to below 1%, but not zero. For HIV-infected individuals receiving antiretroviral therapy with a persistently low viral load, breastfeeding should be supported if they choose this method. If viral load is not suppressed, pasteurized donor breast milk or formula is recommended.
◉ Impact on Breastfed Infants
Thirteen mothers breastfed while receiving efavirenz 600 mg/day, lamivudine 150 mg, and zidovudine 300 mg/day (n = 12) or stavudine 60 mg/day (n = 1). Six months after breastfeeding, none of the infants reported any adverse reactions, were HIV-free, and developed normally. A non-blinded study in Uganda compared the outcomes of breastfed infants and their HIV-positive mothers. The mothers were randomly assigned to receive antiretroviral therapy with either efavirenz 600 mg/day or lopinavir 400 mg plus ritonavir 100 mg/day twice daily. All mothers received lamivudine 150 mg, zidovudine 300 mg twice daily, and sulfamethoxazole-trimethoprim once daily. All infants received prophylactic treatment with zidovudine for one week or nevirapine for six weeks, and sulfamethoxazole-trimethoprim from six weeks of age until six weeks after weaning. Almost all infants were exclusively breastfed until six months of age, and approximately 73% were partially breastfed until 12 months of age. There were no statistically significant differences between the two groups in hospitalization rates or adverse events (including anemia, neutropenia, or death).
In 32 breastfed infants (feeding extent unspecified), whose mothers received 600 mg efavirenz daily as part of a multidrug combination therapy for HIV infection, no adverse events were observed in the infants at 1, 3, and 6 months of age, and no adverse events were reported by the mothers.
A prospective cohort study in Malawi compared infants born to HIV-positive mothers (n = 260) receiving efavirenz and tenofovir disoproxil fumarate with infants born to HIV-negative mothers (n = 125). Infant growth and development were followed for up to 18 months, at which time there were 169 mother-infant pairs in the treatment group and 54 mother-infant pairs in the HIV-negative group. In an open-label, controlled, multicenter phase 3 clinical trial, no difference in growth and development was found between infants breastfed by treated mothers and infants breastfed by untreated mothers. Women diagnosed with HIV were randomly assigned to receive one of three treatment regimens: dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (n = 208); dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (n = 202); or efavirenz, emtricitabine, and tenofovir disoproxil fumarate (n = 207). Treatment began between 14 and 28 weeks of gestation and continued postpartum. Of the 617 live births, 99% were still breastfeeding at the time of their last HIV test, which was performed no later than 50 weeks of age. The mean duration of infant participation in the study was 47.6 weeks. The proportion of infants experiencing grade 3 or higher clinical or laboratory adverse events ranged from 25% to 31%, but there was no statistically significant difference between the groups. Compared to efavirenz, emtricitabine, and tenofovir disoproxil fumarate, dolutegravir-containing treatment regimens reduced virological failure rates, HIV resistance rates, and infant mortality within 50 weeks postpartum.
◉ Effects on Lactation and Breast Milk
Gynecomastia has been reported in men and at least one woman treated with efavirenz. Efavirenz appears to induce gynecomastia more frequently than other antiretroviral drugs. Gynecomastia initially occurs unilaterally but can progress to bilateral. It usually resolves spontaneously within a year even with continued treatment. The implications of these findings for lactating mothers are unclear. Prolactin levels in mothers who have established lactation may not affect their ability to breastfeed.

[1]. HIV-1 reverse transcriptase plus-strand initiation exhibits preferential sensitivity to non-nucleoside reverse transcriptase inhibitors in vitro. J Biol Chem. 2007 Mar 16;282(11):8005-10.

[2]. L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother. 1995 Dec;39(12):2602-5.

[3]. Differential susceptibility of HIV-1 reverse transcriptase to inhibition by RNA aptamers in enzymatic reactions monitoring specific steps during genome replication. J Biol Chem. 2006 Sep 1;281(35):25712-22.

C14H9CLF3NO2

315.674973249435

315.027

177530-93-7

3203

Typically exists as solid at room temperature

3.522

1

5

1

21

519

0

ClC1=CC=2C(C(F)(F)F)(C#CC3CC3)OC(NC2C=C1)=O

XPOQHMRABVBWPR-UHFFFAOYSA-N

InChI=1S/C14H9ClF3NO2/c15-9-3-4-11-10(7-9)13(14(16,17)18,21-12(20)19-11)6-5-8-1-2-8/h3-4,7-8H,1-2H2,(H,19,20)

6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one

Racemic-EfavirenzRac-Efavirenz L 741211 L-741211 L741211

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)