Metabolism / Metabolites
Hepatic metabolism. Biological half-life 20 hours at an 800 mg dose.

[1]. Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition

[2]. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum

(+)-Caranolactone A is an organic heterotetracyclic compound with the structure 11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2',3'-h]chromen-2-one, substituted with a hydroxyl group at position 12, methyl groups at positions 6, 6, 10, and 11, and a propyl group at position 4 (10R,11S,12S stereoisomers). This compound, isolated from Calophyllum lanigerum var. austrocoriaceum and Calophyllum brasiliense, exhibits potent activity against HIV-1 reverse transcriptase. It is both an HIV-1 reverse transcriptase inhibitor and a plant metabolite. It is an organic heterotetracyclic compound belonging to the δ-lactone, cyclic ether, and secondary alcohol classes. Caranolactone A is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) derived from a plant found in the Malaysian rainforest. A related compound, caranolide B, also exhibits anti-HIV activity. Both drugs were developed by Sarawak Pharmaceuticals. A preliminary dose study in HIV-infected individuals showed that both drugs had significant antiviral effects compared to placebo. Caranolide A has been reported to be found in Calophyllum lanigerum, Calophyllum teysmannii, and Calophyllum brasiliense, with relevant data available. Drug Indications For combination therapy of HIV infection (AIDS). Mechanism of Action Viral life cycle studies indicate that caranolide A acts in the early stages of infection, similar to the known HIV reverse transcriptase (RT) inhibitor 2',3'-dideoxycytidine. In enzyme inhibition assays, caranolide A effectively and selectively inhibited recombinant HIV-1 reverse transcriptase within the tested concentration range, but had no inhibitory effect on cellular DNA polymerase or HIV-2 reverse transcriptase.

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Pharmacodynamics
Caranolactone A is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) extracted from a plant found in the Malaysian rainforest. Its related compound, caranolactone B, also possesses anti-HIV activity. Both drugs were developed by Sarawak Pharmaceuticals. The drug is metabolized by cytochrome P450 CYP3A, and its developers believe that combination therapy with ritonavir (Novil) can increase drug concentrations. The drug is active in vitro against HIV viruses carrying the two most common NNRTI-related mutations (K103N and Y181C), and its selective mutations do not generate cross-resistance with other NNRTIs under investigation. A substitution of the reverse transcriptase Y188H codon is associated with a 30-fold increase in in vitro resistance to caranolactone A (Quan 1999). The compound is largely ineffective against the less common type 2 HIV strains.

C22H26O5

370.44

370.178

142632-32-4

64972

Typically exists as solid at room temperature

1.181g/cm3

514.8ºC at 760mmHg

177.2ºC

2E-11mmHg at 25°C

1.558

Originated from plants: Calophyllaceae Calophyllum lanigerum Miq.

4.38

1

5

2

27

666

3

CCCC1=CC(=O)OC2=C1C3=C(C=CC(C)(C)O3)C4=C2[C@H]([C@H](C)[C@@H](C)O4)O

NIDRYBLTWYFCFV-FMTVUPSXSA-N

InChI=1S/C22H26O5/c1-6-7-13-10-15(23)26-21-16(13)20-14(8-9-22(4,5)27-20)19-17(21)18(24)11(2)12(3)25-19/h8-12,18,24H,6-7H2,1-5H3/t11-,12-,18+/m1/s1

(16R,17S,18S)-18-hydroxy-10,10,16,17-tetramethyl-6-propyl-3,9,15-trioxatetracyclo[12.4.0.02,7.08,13]octadeca-1(14),2(7),5,8(13),11-pentaen-4-one

NSC 675451; NSC675451; NSC-675451

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.)