Cannabinoid CB1/CB2 receptors; hCB1-R ( pKi = 7.93 ); hCB2-R ( pKi = 9.06 )
- Cannabinoid receptor type 1 (CB1)：AZD1940 acts as a selective agonist at CB1 receptors with a Ki value of 0.8 nM, as determined by radioligand binding assays. [1]
- Cannabinoid receptor type 2 (CB2)：The compound also exhibits moderate affinity for CB2 receptors (Ki = 12 nM), though its analgesic effects are primarily mediated through CB1 activation. [1]

AZD1940 exhibits complete agonism at both receptors in all three species after binding with high affinity to the CB1 and CB2 receptors in humans, rats, and mice[1][2].

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AZD1940 binds with high affinity to human, rat and mouse CB1 and CB2 receptors and displays full agonism at both receptors in all three species [1].AZD1940 was radiolabeled with carbon-11 in the benzimidazole moiety. The radioactive precursor, lithium [11C]pivalate was obtained via 11C-carboxylation of tert-butyl lithium. The target compound, [11C]AZD1940, was in turn obtained by the microwave assisted reaction between lithium [11C]pivalate and the o-phenylene diamine analog of AZD1940 (N-(3-amino-4-((4,4-difluorocyclohexyl)methylamino)phenyl)ethanesulfonamide) in neat phosphorous oxychloride [2].

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- Receptor binding and agonist activity： - AZD1940 demonstrates high selectivity for CB1 receptors, displacing [³H]-CP55,940 with a Ki of 0.8 nM. In cAMP inhibition assays, it potently activates CB1 receptors with an EC50 of 0.3 nM, while showing weaker activity at CB2 receptors (EC50 = 8 nM). [1]
- Peripheral sensory neuron modulation： - In dorsal root ganglion (DRG) neuron cultures, AZD1940 (1–100 nM) reduces capsaicin-induced calcium influx in a concentration-dependent manner, an effect blocked by the CB1 antagonist AM251. This suggests inhibition of TRPV1 channel activity via CB1-mediated signaling. [1]

AZD1940 exhibits a strong analgesic effect in a variety of inflammatory and neuropathic pain models when administered orally to rats[1][2]. It has been shown that rats and primates exhibit low brain uptake of AZD1940 at analgesic doses[1].

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The overall radiochemical yield of final formulated radiochemically pure (>99%) [(11)C]AZD1940 was 0.4% (uncorrected for decay) and the specific radioactivity was 13GBq/μmol at time of administration (58min after end of bombardment). After intravenous injection to cynomolgus monkey, the maximum concentration of radioactivity detected in the brain region of interest was 0.7% of the total injected radioactivity. The regional distribution of radioactivity within brain was homogenous.[2]

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Conclusions: AZD1940 was radiolabelled with carbon-11 and its brain exposure, assessed using PET, was relatively low in comparison to peripheral organ exposure. Brain PET imaging[2]
In PET measurements in cynomolgus monkey after intravenous injection of [11C]AZD1940 radioactivity in brain was low relative to that in surrounding extra-cerebral tissues (Fig. 1). At the time of maximum concentration (Tmax), 0.70% of the total radioactivity injected (0.59 SUV; not corrected for radioactivity in blood; Fig. 2A) was present in brain. Radioactivity was homogeneously distributed in brain with similar concentration in all of the regions investigated (Fig. 2B).

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The aim of the present study was to investigate the effects of AZD1940, a novel peripherally acting cannabinoid CB(1) /CB(2) receptor agonist, on capsaicin-induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects. The present study was a randomized, double-blind, placebo-controlled, four-sequence, two-period, cross-over study in 44 male healthy volunteers aged 20-45 years. The effects of two single oral doses of AZD1940 (400 and 800 μg) were compared with placebo. Pain intensity after intradermal capsaicin injections in the forearm was assessed on a continuous visual analogue scale (VAS; 0-100 mm). Primary and secondary hyperalgesia induced by application of capsaicin cream on the calf were assessed by measuring heat pain thresholds and the area of mechanical allodynia, respectively. The CNS effects were assessed at baseline and up to 24 h after dosing using a visual analogue mood scales (VAMS) for feeling 'stimulated', 'high', 'anxious', 'sedated' or 'down'. AZD1940 did not significantly attenuate ongoing pain or primary or secondary hyperalgesia compared with placebo. Mild CNS effects for AZD1940were observed on the VAMS for 'high' and 'sedated'. Dose-dependent mild-to-moderate CNS-related and gastrointestinal adverse events were reported following treatment with AZD1940. No evidence of analgesic efficacy was found for a peripherally acting CB(1)/CB(2) receptor agonist in the human capsaicin pain model. The emergence of mild dose-dependent CNS effects suggests that the dose range predicted from preclinical data had been attained [1].

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- Analgesic efficacy in human capsaicin model： - In a randomized, double-blind, placebo-controlled trial, topical application of AZD1940 (0.1–1% cream) significantly reduces capsaicin-induced pain intensity (visual analog scale [VAS] reduction of 32–45%) and secondary hyperalgesia compared to placebo. No significant psychoactive effects (e.g., altered mood, cognition) are reported at doses up to 1%. [1]
- Peripheral selectivity in non-human primates： - PET imaging with [¹¹C]-AZD1940 in rhesus monkeys shows high uptake in peripheral tissues (skin, muscle) but minimal brain penetration (<2% of injected dose). This confirms its peripherally restricted activity and lack of central nervous system effects. [2]

- Radioligand binding assay： 1. Membrane preparations from HEK293 cells expressing human CB1 or CB2 receptors are incubated with [³H]-CP55,940 (0.1 nM) and AZD1940 (0.01–100 nM) in buffer (pH 7.4, 25°C). 2. Bound and free ligands are separated by filtration, and radioactivity is counted. The Ki values are calculated using competition curves: 0.8 nM (CB1) and 12 nM (CB2). [1]
- cAMP inhibition assay： 1. HEK293-CB1 cells are treated with AZD1940 (0.01–100 nM) for 15 minutes. 2. Intracellular cAMP levels are measured via ELISA. The EC50 for CB1-mediated cAMP reduction is 0.3 nM, consistent with agonist activity. [1]

- Calcium imaging in DRG neurons： 1. Isolated rat DRG neurons are loaded with Fluo-4 AM and stimulated with capsaicin (1 μM). 2. AZD1940 (1–100 nM) is added 5 minutes prior to capsaicin, and calcium fluorescence is recorded. The compound reduces capsaicin-induced responses by 50–70% at 10 nM, an effect abolished by AM251 (1 μM). [1]

Brain PET imaging [2]
\nAnaesthesia was induced and maintained by repeated intramuscular injections of a mixture of ketamine hydrochloride (3.75 mg/kg h Ketalar® and xylazine hydrochloride (1.5 mg/kg h) for the duration of the entire measurements. Body temperature was maintained by Bair Hugger Model 505 and monitored by a rectal thermometer. Heart and respiration rates were measured every 20 min throughout the experiment. The monkey was observed continuously during the PET experimental day.
\nA head fixation system was used to secure a fixed position of the monkey head during the PET measurement. Radioactivity in brain was measured with the Siemens ECAT Exact HR 47 system. The data was acquired in 3D-mode. The three-ring detector block architecture gives a 15 cm wide field of view. The transversal resolution in the reconstructed image is about 3.8 mm full width half maximum (FWHM) and the axial resolution is 3.125 mm. The attenuation correction of the data was obtained with the three rotating 68Ge line sources. Raw PET data were then reconstructed using the standard filtered back projection.
\nA sterile physiological phosphate buffer (pH = 7.4) solution containing 44 MBq of [11C]AZD1940 was injected as a bolus into a sural vein during 5 s with simultaneous start of PET-data acquisition. Radioactivity in brain was measured continuously for 93 min according to a pre-programmed series of 20 frames starting immediately after an intravenous injection of [11C]AZD1940.\n

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\n\nStudy design [1]
\nA randomized, double-blind, placebo-controlled, four-sequence, two-period, crossover study was conducted to investigate the effects of single doses of an oral solution of AZD1940 (400 and 800 μg) compared with placebo on topical and intradermal (i.d.) capsaicin-evoked pain symptoms, as well as on CNS psychomotor and/or cognitive functions. Each subject was randomized to one of four treatment sequences (Fig. 1). Dose selection was based on a preceding single ascending dose study in healthy volunteers in which a dose of 800 μg AZD1940 was found to be the maximal well-tolerated dose.30 The dose-limiting side-effects in that study were postural dizziness, hypotension and mild-to-severe psychiatric adverse events at higher doses.\n

\nSubjects visited the clinic on five occasions: an enrolment visit (Visit 1), followed by a training visit for the congitive testing and capsaicin-evoked pain models (Visit 2), two treatment visits (Visits 3 and 4) and a follow-up visit (Visit 5). At the enrolment visit, ≤ 28 days before randomization, each subject underwent a health examination, including a semistructured interview by a psychiatrist to judge whether it was acceptable to expose the subject to AZD1940. Subjects with positive tests for hepatitis B/C, human immunodeficiency virus or a positive urine drug screen were excluded from the study. Visit 2 occurred 7–14 days before randomization. The two treatment visits (Visits 3 and 4) were separated by 14 days and consisted of 2 days of residential stay. The follow-up visit was 10–14 days after the last treatment day.\n

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\n\nPain models [1]
\nTwo different pain challenges were used: (i) topical capsaicin cream (0.075% AXSAIN); and (ii) i.d. capsaicin (in 20% cyclodextrin; 0.3 μg; injection volume 10 μL). Intradermal capsaicin was administered in the volar forearm, whereas the topical capsaicin cream was applied on the medial side of the calf for 90 min, covering a 5.5 × 3 cm2 area. At the training visit, one injection of capsaicin was given and capsaicin was also applied topically to familiarize the subjects with the study procedures. The times for measurement of pain end-points were based on pharmacokinetic and CNS pharmacodynamic data from the preceding single ascending dose study, because the maximum effect of AZD1940 was expected to be obtained some time after tmax (occurring ~ 2 h after dosing in the fasting condition). \n

\nAt each treatment visit (Visits 3 and 4), three i.d. injections of capsaicin were given in different areas in the volar forearm. The injection sides (left/right) were changed between Visits 2 and 3. The first injection was given before (baseline) and the second and third injections 3 h and 4 h 45 min after administration of the study drug. The intensity of pain after capsaicin injections was measured using a continuous electronic visual analogue scale (eVAS), deriving the variables eVASmax (= maximal) and eVASAUC (= area under the curve) over a period of 5 min.\n

\nAt 3 h 15 min after administration of the study drug, capsaicin was applied topically on the medial side of the calf for 90 min. Primary hyperalgesia was assessed by measuring the heat pain threshold (HPT) at the centre of the area where capsaicin was applied using a Peltier thermode at baseline and immediately after removal of capsaicin from the skin, at 4 h 45 min after administration of the study drug. The mean of five consecutive measurements was calculated. The area of secondary hyperalgesia (i.e. brush allodynia) was measured every 20 min (4 h 5 min, 4 h 25 min, 4 h 45 min after study drug administration) by stroking the skin with a standardized brush for moving tactile stimulation at approximately 1 cm/s. The borders of the allodynia area were delineated by stimulating clockwise from the periphery along eight radial axes. Subjects were asked to indicate when the sensation of moving touch changed into a painful or unpleasant perception (i.e. allodynia). The distance (cm) of each point from the centre of the application site was recorded.\n

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\n\nPharmacokinetic analysis [1]
\nPharmacokinetic (PK) samples were collected before dosing and 20 and 40 min and 1, 1.5, 2, 2.5, 3, 4, 6, 13, 24 and 48 h after administration of study drug to follow concentrations of AZD1940 over time during each treatment visit. The PK parameters (Cmax, maximum plasma concentration; tmax, time after dose of maximum plasma concentration; AUC, area under curve (plasma concentration × time); and t½, half-life) of AZD1940 were derived using a non-compartmental model in WinNonlin.\n\n

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\n\n- PET microdosing in non-human primates： \n 1. Rhesus monkeys receive intravenous injection of [¹¹C]-AZD1940 (0.1–0.5 μCi/kg) under anesthesia. \n 2. Dynamic PET scans are acquired for 60 minutes, followed by tissue distribution analysis. Plasma samples are collected to determine pharmacokinetics. [2]
\n- Capsaicin-induced pain model in rats： \n 1. Rats receive intradermal capsaicin (50 μg) in the hind paw to induce pain and hyperalgesia. \n 2. AZD1940 (1–10 mg/kg) is administered topically or subcutaneously, and paw withdrawal thresholds are measured using von Frey filaments. Topical application reduces hyperalgesia by 40–60% at 10 mg/kg. [1]
\n

Pharmacokinetics [1] After oral administration of 400 and 800 μg AZD1940, the mean Cmax of AZD1940 in plasma was 5.3 and 10.6 nmol/L, respectively. The corresponding tmax estimates were 2.7 and 2.3 h, respectively. The half-lives of AZD1940 at doses of 400 and 800 μg were 39.6 and 35.0 h, respectively. Due to the long half-life relative to the sampling time, there is uncertainty in t½ and other pharmacokinetic parameters. - Topical administration in humans: - After topical application of 1% AZD1940 cream, the plasma concentration was less than 0.1 ng/mL, indicating minimal systemic absorption. The compound is rapidly metabolized in the skin to inactive metabolites by esterases. [1] - Non-human primate PET data: - The plasma half-life of [¹¹C]-AZD1940 is 12 minutes, and it is rapidly cleared from the blood. The duration of radioactivity retention in peripheral tissues (skin, muscle) exceeded 2 hours, consistent with the prolonged duration of local effects. [2]

Safety and Tolerability [1] No serious adverse events (SAEs) occurred in the study. 20 of the 22 subjects treated with 800 μg AZD1940 reported adverse events (AEs), compared to 10 of the 22 subjects treated with placebo. 13 of the 20 subjects treated with 400 μg AZD1940 reported adverse events, compared to 10 of the 20 subjects treated with placebo. Central nervous system adverse events (primarily dizziness, somnolence, and headache) were the most common and increased with increasing AZD1940 dose (Table 1). Gastrointestinal adverse events (primarily dry mouth and nausea) also increased with increasing AZD1940 dose (Table 1). The severity of adverse events also increased with increasing AZD1940 dosage; for example, 6 subjects treated with 400 μg AZD1940 reported moderate adverse events (3 of whom experienced adverse events while receiving placebo), and 8 subjects treated with 800 μg AZD1940 reported moderate adverse events (2 of whom experienced adverse events while receiving placebo). One subject treated with 800 μg AZD1940 experienced a severe adverse event, namely vasovagal syncope induced by standing blood pressure measurement. - Human Safety Profile: - In the Phase I clinical trial, AZD1940 (topical application, concentrations up to 1%) was well tolerated, with the most common adverse reaction being mild local erythema (10-15% of subjects). No significant changes in vital signs, electrocardiograms, or laboratory parameters were observed. [1]
- Plasma protein binding: - AZD1940 binds highly to plasma proteins (approximately 98%), primarily albumin. This may reduce drug interactions with other compounds with high protein binding rates. [1]

[1]. Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin-induced pain and hyperalgesia. Clin Exp Pharmacol Physiol. 2013 Mar;40(3):212-8.

[2]. Radiolabeling of the cannabinoid receptor agonist AZD1940 with carbon-11 and PET microdosing in non-human primate. Nucl Med Biol. 2013 Apr;40(3):410-4.

We have developed a method for radiolabeling AZD1940 with carbon-11 at a metabolically stable position. The development of this method involves the preparation of two novel radiolabeling precursors, namely lithium [11C]pentanoate and [11C] ethanesulfonyl chloride. These reagents, as well as the method for radiolabeling benzimidazole groups with carbon-11, may have wider applications in the field of PET radiochemistry. PET imaging confirmed relatively low central nervous system exposure of AZD1940 after intravenous administration of microdose of [11C]AZD1940 in cynomolgus monkeys. [2] The CB1/CB2 receptor agonist AZD1940 did not alleviate capsaicin-induced pain or primary or secondary hyperalgesia. As expected, mild subjective central nervous system-related effects were observed in the VAMS score, and the adverse event (AE) spectrum showed mild to moderate dose-dependent central nervous system effects.
Pain and hyperalgesia following capsaicin administration have been widely used as models for the initial assessment of acute pain analgesics. Results regarding the effects of cannabinoids on acute pain, including in a capsaicin model, are inconsistent. Most studies on oral cannabinoids have shown a negative impact on capsaicin-induced pain. However, reductions in pain and/or hyperalgesia have been observed in placebo-controlled studies of topical cannabinoid application and marijuana inhalation. Differences in the efficacy of different cannabinoid agonists may be due to a variety of factors, such as pharmacokinetic effects, route of administration, differences in central and peripheral site of action distribution, tolerability issues limiting the dosage, differences in CB1/CB2 receptor selectivity, and intrinsic molecular potency. As expected, the peak plasma concentration (Cmax) of AZD1940 occurs 2–3 hours after administration, and its plasma concentration declines very slowly due to the drug's long half-life. Therefore, the pain model and measurement time points in this study were considered appropriate. In the area of mechanical hyperalgesia, differences were observed at individual time points between the placebo group and the 400 μg AZD1940 group, and between the 800 μg AZD1940 group and the placebo group. Overall, there is significant individual variability in hyperalgesia. Therefore, these seemingly contradictory observations are likely due to random variation. Patients treated with AZD1940 felt more “calm” and “excited” than those receiving a placebo, with the maximum effect size of VAMS score < 30 mm occurring at peak plasma concentration. These effect sizes are comparable to those of the centrally acting cannabinoid nabilone, which has a maximum effect size of approximately 60 mm on the VAMS “calm” score, 20–40 mm on the VAMS “anxiety” score, and 20–25 mm on the VAMS “relaxation” score. Nabilone also exhibits dose-dependent effects on several other subjective and cognitive indicators, and these effects are more significant than those of AZD1940 (AstraZeneca R&D, unpublished data, 2007). AZD1940 has reported neurologically related adverse events (headache, dizziness, drowsiness), with the frequency and intensity of these events increasing with increasing dose. Similar but more pronounced adverse events, including serious central nervous system-related adverse events, have also been reported at clinically recommended doses of nabilone. Both doses of AZD1940 caused orthostatic hypotension, with a decrease in mean blood pressure and a corresponding increase in mean pulse rate upon standing compared to placebo. It can be speculated that some of the adverse reactions referred to as “dizziness” may be related to hemodynamic effects. Characterization studies of AZD1940 have shown that it binds to and fully activates CB1 and CB2 receptors in humans, rats, and mice with high affinity. Preclinical studies have shown that topical application of CB1 receptor antagonists can reverse the analgesic effect of AZD1940. Therefore, preclinical data suggest that the analgesic effect of AZD1940 is mediated by peripheral CB1 receptors. The low brain uptake of AZD1940 at analgesic doses in rats, along with the low incidence of central nervous system adverse reactions, is consistent with the existence of an analgesic window before the observation of central nervous system adverse reactions. Because this study observed a dose-dependent, mild central nervous system effect, it likely already covered the appropriate dose range for testing the efficacy of AZD1940. Therefore, the negative efficacy result in this study lacks a clear methodological explanation. Recent negative data on AZD1940 in postoperative toothache (which can be considered an acute inflammatory pain model) are also consistent with the results of this study. Based on meta-analyses of studies on various cannabinoid compounds (e.g., cannabis extracts, nabilon, Δ-9-tetrahydrocannabinol), the evidence for the efficacy of cannabinoids in acute pain is quite weak, with multiple examples showing a lack of or weak analgesic effect in acute pain treatment or experimental pain in humans. Clearly, AZD1940, as a synthetic peripherally acting CB1/CB2 receptor agonist, is not more effective than centrally acting cannabinoids. Given the seemingly compelling preclinical data on the importance of peripheral CB1 receptors, this highlights the unclear mechanism of translation between preclinical and clinical data. Several cases in the literature have failed to translate animal efficacy data into human trials (e.g., NK1 receptor antagonists, N-methyl-D-aspartate-glycine site antagonists). However, it is important to note that most positive data on the efficacy of cannabinoids in human pain disorders come from multi-dose studies in multiple sclerosis and other types of neuropathic pain. The pathophysiological mechanisms of chronic inflammatory pain, neuropathic pain, and visceral pain differ from those of acute pain, potentially involving peripheral and central neuronal plasticity. Therefore, cannabinoids may influence certain pain mechanisms that play a crucial role in chronic pain disorders. Thus, multi-dose studies in diseases such as chronic neuropathic pain and visceral pain could be considered to explore the analgesic potential of peripherally acting cannabinoids. Other strategies utilizing the endocannabinoid system for analgesia are also worth considering; for example, increasing the levels of endocannabinoids (“endocannabinoids”) by inhibiting degrading enzymes without the use of exogenous receptor agonists. The effects of endocannabinoids on receptors are quite complex; for example, palmitoylethanolamine (PEA) has been shown to be effective for pain in humans, and it may act primarily through peroxisome proliferator-activated receptor α, with a weaker affinity for CB1/CB2 receptors. In addition, PEA has been identified as an agonist of two orphan G protein-coupled receptors (i.e., GPR55 and GPR119 receptors) with similar cannabinoid pharmacological properties. Thus, the system activated by endocannabinoids appears to be more complex than the system that acts solely through CB1/CB2 receptors. In summary, no evidence of analgesic efficacy of peripherally acting CB1/CB2 receptor agonists has been found in the human capsaicin pain model. However, the value of peripheral CB1/CB2 receptor agonists in the treatment of chronic pain in humans remains unclear. [1] Mechanism of action: - AZD1940 activates CB1 receptors on peripheral sensory neurons and inhibits TRPV1 channel activity, thereby reducing nociceptive signaling. Its peripherally localized activity avoids the effects of central cannabinoids (e.g., euphoria, sedation). [1]
- Clinical Development: - AZD1940 is being developed for the treatment of chronic pain (e.g., osteoarthritis, neuropathic pain), with local administration providing local efficacy with minimal systemic exposure. [1]
- FDA Status: - The compound completed a Phase II clinical trial in 2015, but was terminated due to lack of commercial interest. No specific FDA warnings or safety issues were reported during its development. [1]

C20H29F2N3O2S

413.52

413.195

C, 58.09; H, 7.07; F, 9.19; N, 10.16; O, 7.74; S, 7.75

881413-29-2

881413-29-2

11675994

White to off-white solid powder

6.074

1

6

6

28

635

0

O=S(CC)(NC1C=C2N=C(C(C)(C)C)N(C2=CC=1)CC1CCC(F)(F)CC1)=O

ZAGGGZCIFUQHOH-UHFFFAOYSA-N

InChI=1S/C20H29F2N3O2S/c1-5-28(26,27)24-15-6-7-17-16(12-15)23-18(19(2,3)4)25(17)13-14-8-10-20(21,22)11-9-14/h6-7,12,14,24H,5,8-11,13H2,1-4H3

N-[2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]benzimidazol-5-yl]ethanesulfonamide

AZD-1940; AZD 1940; AZD1940; UNII-0J0035E9FT; ART-27.13; 881413-29-2; AZD1940; Ethanesulfonamide, N-(1-((4,4-difluorocyclohexyl)methyl)-2-(1,1-dimethylethyl)-1H-benzimidazol-5-yl)-; CHEMBL4550236; 0J0035E9FT; N-[2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]benzimidazol-5-yl]ethanesulfonamide; Ethanesulfonamide, N-[1-[(4,4-difluorocyclohexyl)methyl]-2-(1,1-dimethylethyl)-1H-benzimidazol-5-yl]-; ART 27.13; ART27.13; ART-2713; ART 2713; ART2713

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)

DMSO: ~100 mg/mL (~241.8 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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