Bergamotene (5-methoxypsoralen, 5-MOP) concentrations ranged from 0.05 to 25 mM, however there was no change in N-acetyltransferase (NAT) activity in SC-M1 cells between these levels. There was a noticeable dose-dependent effect (r = 0.5687). In COLO 205 cells, bergamotenol at low concentrations (0.05 mM and 0.5 mM) boosted NAT activity, but at high levels (50 mM), it decreased. At our experimental concentration (r=0.8912), bergamotene exhibited a dose-dependent effect on COLO 205 cells: a high dose (50 mM) exhibited a promoting effect, a low dose (0.05~0.5 mM) exhibited an inhibitory effect, and a 5~25 There is no statistically significant difference between the mM concentration and the control protocol [1]. In animals lacking osteoprotegerin, bergapten (5-Methoxypsoralen) inhibits osteoporosis associated with diabetes via controlling the PI3K/AKT, JNK/MAPK, and NF-κB signaling pathways. It has also been demonstrated that bergamotene considerably reduces the synthesis of cytokines that promote inflammation. By preventing the activation of the PI3K/AKT, JNK/MAPK, and NF-κB signaling pathways as well as RANKL-RANK signaling, bergapten can prevent osteoclast differentiation and preserve trabecular integrity [2].

The rat colon has a higher NAT metabolic activity than the stomach, and within 24 hours, bergamot lactone (5-Methoxypsoralen, 5-MOP) lowers the AF content in the stomach. The stomach and intestines have lower AAF concentrations. While DMSO (solvent) had an impact on AAF metabolism, bergamot lactone further boosted AAF metabolism and decreased both the 24-hour stomach and colonic AAF concentrations in comparison to the control regimen. A 24-to 72-hour timeframe is involved [1].

Absorption, Distribution and Excretion
Micronized bergapten in capsules was absorbed slowly by volunteers (time to max serum concn 3.2 hr; elim half-time about 1 hr). When injected iv into rabbits, elim half-time 1-2 min (alpha-phase) & 15 min (beta-phase).
5-Methoxypsoralen showed a high binding affinity to serum proteins & 98-99% was protein bound. Its high binding affinity resulted in higher tissue concn. In the epidermis, it appeared to be bound to independent & noninteracting sites.
Enrichment in epidermis of 5-methoxypsoralen was measured. It was concentrated by human epidermis & concn reached within the tissue was 10-500 times higher than concn of substance in surrounding buffer. The partitioning distribution among tissue components could account for its behavior.
In young adult Hartley guinea-pigs, a linear relation was found between serum and epidermal concn of 5-methoxypsoralen, and the observed skin phototoxicity correlated with the serum 5-methoxypsoralen concn ... .
For more Absorption, Distribution and Excretion (Complete) data for 5-Methoxypsoralen (11 total), please visit the HSDB record page.

---

Metabolism / Metabolites
PURPOSE: To discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity. METHODS: Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor. RESULTS: a total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation. Five toxicophoric substructures were shared among psoralen, bergapten and their corresponding metabolites; one toxicophoric marker (resorcinol) was only identified in bergapten and its biotransformation products. CONCLUSION: Although the toxic effects of psoralens are well known and documented, there is little information concerning the role of their metabolites in this process. We believe this work add to the knowledge of which molecular substructures are relevant to the process of metabolism and toxicity induction, thus guiding the search and development of more effective and less toxic drugs to treat vitiligo.
A number of studies have demonstrated that cytochrome P450 (P450) converts furanocoumarin derivatives into reactive molecules, which form covalent bonds to biomolecules. 5-Methoxypsoralen (5-MOP) is a natural furanocoumarin from apiaceous plants. In this study, we examined the effect on 5-MOP metabolism of single nucleotide polymorphisms (SNPs) in CYP2A13. We used Escherichia coli-generated recombinant enzymes of wild-type CYP2A13*1 and five variants, CYP2A13*4 (R101Q), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9 (V323L). In high-performance liquid chromatography analyses of 5-MOP metabolic products, CYP2A13*1 converted 5-MOP into 5-MOP dihydrodiol; K(m) and V(max) values of the reaction were 1.44 +/- 0.17 uM and 4.23 +/- 0.36 nmol/(min x nmol P450), respectively. The generation of a dihydrodiol from 5-MOP implies that conversion by CYP2A13 causes toxicity due to the formation of covalent bonds with DNA or proteins. Most of the CYP2A13 variants could metabolize 5-MOP; K(m) values for CYP2A13*5, *6, *8, and *9 were 1.63 =/- 0.12, 1.36 +/- 0.10, 0.85 +/- 0.09, and 0.58 +/- 0.06 uM, respectively, and V(max) values were 3.20 +/- 0.13, 4.69 +/- 0.13, 2.34 +/- 0.07, and 1.84 +/- 0.09 nmol/(min x nmol P450), respectively. However, the processing of 5-MOP by CYP2A13*4 was not detectable. Based on this data, we hypothesize that SNPs within the CYP2A13 gene affect metabolism of 5-MOP in humans.
Bergapten has known human metabolites that include Unii-3abk64HG9O.

---

Biological Half-Life
Micronized bergapten in capsules was absorbed slowly by volunteers (time to max serum concn 3.2 hr; elim half-time about 1 hr).
When injected iv into rabbits, elim half-time 1-2 min (alpha-phase) & 15 min (beta-phase).

Toxicity Summary
IDENTIFICATION AND USE: 5-Methoxypsoralen (5-MOP) is a furocoumarin. As a component of bergamot oil, 5-MOP is present in some perfumes and fragrances, sunscreen preparations and food products. It has been used to promote tanning in suntan preparations. 5-MOP, in combination with UVA, is commonly used as a photochemotherapeutic agent for the treatment of psoriasis. HUMAN STUDIES: Photochemotherapy is very effective for the treatment of skin diseases such as psoriasis, as well as for the prophylactic 'hardening' therapy of patients suffering from polymorphic light eruption. The photosensitizers most widely used for oral photochemotherapy are the furocoumarins. Beside light-induced phototoxic reactions due to the photosensitizing activity of psoralens, side-effects after the oral intake of psoralens are nausea and vomiting, headaches, anxiety and sleeplessness. Anaphylaxis to 5-MOP has been reported. A 55-year-old woman with psoriasis vulgaris was treated with oral 5-MOP and UVA photochemotherapy. After 40 treatments over 3 months she became unwell with hepatitis attributable to the psoralen. 5-MOP caused chromosomal damage in human cells in vitro. ANIMAL STUDIES: When 5-MOP was given orally to beagle dogs at daily doses of 100 or 400 mg/kg (8 days), 60 mg/kg (28 days) or 48 mg/kg (26 wk), at the highest doses tested there were delayed signs of behavioral toxicity, bullous dermatitis, bilateral keratitis, decreased food consumption and decreased weight gain. The cutaneous lesions were reversible, whereas the ocular lesions were not. Hepatomegaly, necrosis and hepatic inflammation occurred in the 48-mg/kg dose group. 5-MOP plus UVA and 12-O-tetradecanoylphorbol 13-acetate induced skin carcinomas in mice. Rats were dosed daily with 5-MOP (75 or 150 mg/kg, p.o.), or vehicle control. Treated males had significantly smaller pituitary glands, fewer sperm per ejaculate, and fewer sperm in the vasa deferentia and epididymides than controls. Dosing significantly elevated levels of testosterone and increased relative testis weight, but did not directly affect testicular weight. Females bred to dosed males required more time to become pregnant, and these males required more breeding attempts. Female rabbits were given 5-MOP orally at daily doses of 0, 70 or 560 mg/kg bw on days 7-18 of gestation. With 560 mg/kg, there was maternal toxicity and a dose-dependent increase in fetal abnormalities. 5-MOP formed a noncovalently-bound complex with DNA in vitro in the dark. It photobound covalently to DNA in vitro in Saccharomyces cerevisiae and in Chinese hamster V79 cells. It photoinduced interstrand cross-links in DNA in vitro and in Chinese hamster V79 cells. 5-MOP alone was reported to be mutagenic to Salmonella typhimurium TA100 in the presence or absence of metabolic activation and to Escherichia coli lac- z (ND160). 5-MOP plus UVA reduced survival of repair-deficient mutants of Bacillus subtilis and E. coli, addition of metabolic activator inhibited the lethal activity.

---

Interactions
Sunscreens containing 5-methoxypsoralen (5-MOP) are being promoted commercially to incr suntanning & sun protection. The sunscreen, Sun System III (SS III) which contains 5-MOP plus 20 Joules/sq cm of UV radiation (UVA) caused erythema & delayed pigmentation in the skin. No photoxicity was seen unless the solar simulator output was filtered through water to reduce infrared radiation. This indicates that cutaneous phototoxic reactions to 5-MOP plus UVA are diminished by heat. Use of phototoxic psoralens in sunscreens is inappropriate because of the risk of incr uv-induced skin cancer.
PURPOSE: This study was designed to investigate the potential effect of bergapten on lipopolysaccharide (LPS)-mediated osteoclast formation, bone resorption and osteoclast survival in vitro. METHODS: After osteoclast precursor RAW264.7 cells were treated with bergapten (5, 20, 40 umol/L) for 72 hours in the presence of LPS (100 ng/mL), osteoclastogenesis was identified by tartrate-resistant acid phosphatase (TRAP) staining, and the number of TRAP-positive multinucleated cells [TRAP(+)MNCs] per well were counted. To investigate the effect of bergapten on osteoclastic bone resorption, RAW264.7 cells were treated with bergapten for six days in the presence of LPS, and the area of bone resorption was analyzed with Image Pro-Plus. Next, we examined apoptosis of RAW264.7 cells after bergapten incubation for 48 hours by flow cytometer using annexin V/propidium iodide (PI) double labeling. Finally, osteoclast survival was observed by Hoechst 33342 labeling and Western blotting after bergapten treatment for 24 hours. RESULTS: Data showed that bergapten (5-40 umol/L) dose-dependently inhibited LPS-induced osteoclast formation and bone resorption. Treatment with bergapten triggered apoptotic death of osteoclast precursor RAW264.7 cells in a dose-dependent manner. Furthermore, bergapten significantly reduced the survival of mature osteoclast, as demonstrated by emergence of apoptotic nuclei and activation of apoptotic protein caspase 3/9. CONCLUSIONS: These findings suggest that bergapten effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival via apoptotic response of osteoclasts and their precursors. The study identifies bergapten as an inhibitor of osteoclast formation and bone resorption and provides evidence that bergapten might be beneficial as an alternative for prevention and treatment of inflammatory bone loss.
PURPOSE: Melanoma is an aggressive form of skin cancer. The aim of the study was to evaluate the influence of UVA radiation and psoralens: 5-methoxypsoralen (5-MOP) or 8-methoxypsoralen (8-MOP) on melanoma cells viability. MATERIALS AND METHODS: The amelanotic C32 and melanotic COLO829 human melanoma cell lines were exposed to increasing concentrations of psoralens (0.1-100 uM) in the presence or absence of UVA radiation. Cell viability was evaluated by the WST-1 assay. RESULTS: We demonstrated that 8-MOP, in contrast to 5-MOP, has no cytotoxic effect on both melanoma cell lines. Simultaneous exposure of cells to 8-MOP and UVA radiation caused significant cytotoxic response in C32 cells where the EC50 value was estimated to be 131.0 uM (UVA dose: 1.3 J/sq cm) and 105.3 uM (UVA dose: 2.6 J/cm2). The cytotoxicity of 5-MOP on both C32 and COLO829 cells was significantly augmented by UVA radiation - the EC50 was estimated to be 22.7 or 7.9 uM (UVA dose: 1.3 J/sq cm) and 24.2 or 7.0 uM (UVA dose: 2.6 J/sq cm), respectively. CONCLUSIONS: The demonstrated high cytotoxic response after simultaneous exposure of melanoma cells to psoralens and UVA radiation in vitro suggests the usefulness of PUVA therapy to treat melanoma in vivo.
AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses. METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed. RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 +/- 3940 vs 30 +/- 21, P < 0.05; 6482 +/- 4018 vs 146 +/- 58, P < 0.05; 24627 +/- 10975 vs 1504 +/- 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 +/- 1810 vs 8355 +/- 3940, P < 0.05; 54 +/- 39 vs 8355 +/- 3940, P < 0.05; 19 +/- 9 vs 8355 +/- 3940, P < 0.05), AST levels (IU/L) (729 +/- 685 vs 6482 +/- 4108, P < 0.05; 187 +/- 149 vs 6482 +/- 4108, P < 0.05; 141 +/- 12 vs 6482 +/- 4108, P < 0.05) and LDH levels (IU/L) (7220 +/- 6317 vs 24 627 +/- 10 975, P < 0.05; 1618 +/- 719 vs 24 627 +/- 10 975, P < 0.05; 1394 +/- 469 vs 24 627 +/- 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 +/- 0.45 vs 2.15 +/- 1.07, P > 0.05; 0.59 +/- 0.07 vs 2.15 +/- 1.07, P < 0.05; 0.47 +/- 0.06 vs 2.15 +/- 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 +/- 0.340 vs 3.306 +/- 0.282, P > 0.05; 5.330 +/- 0.421 vs 3.306 +/- 0.282, P < 0.05; 6.180 +/- 0.212 vs 3.306 +/- 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal. CONCLUSION: 5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses.
For more Interactions (Complete) data for 5-Methoxypsoralen (9 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Mice oral 8100 mg/kg bw
LD50 Rats oral >30,000 mg/kg bw
LD50 Guinea-pigs oral 9000 mg/kg bw

[1]. Effects of 5-methoxypsoralen (5-MOP) on arylamine N-acetyltransferase activity in the stomach and colon of rats and human stomach and colon tumor cell lines. In Vivo. 2005 Nov-Dec;19(6):1061-9.

[2]. Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice. Int J Mol Med. 2016 Dec;38(6):1661-1672.

5-Methoxypsoralen with ultraviolet A therapy can cause cancer according to an independent committee of scientific and health experts.
Grayish-white microcrystalline powder or yellow fluffy solid. (NTP, 1992)
5-methoxypsoralen is a 5-methoxyfurocoumarin that is psoralen substituted by a methoxy group at position 5. It has a role as a hepatoprotective agent and a plant metabolite. It is a member of psoralens, a 5-methoxyfurocoumarin and an organic heterotricyclic compound. It is functionally related to a psoralen.
Bergapten is under investigation in clinical trial NCT00533195 (Comparison of UVA1 Phototherapy Versus Photochemotherapy for Patients With Severe Generalized Atopic Dermatitis).
Bergapten has been reported in Caragana frutex, Angelica gigas, and other organisms with data available.
A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS.
See also: Parsley (part of); Anise (part of); Angelica archangelica root (part of) ... View More ...

---

Therapeutic Uses
/EXPL THER/ BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for early stage mycosis fungoides (MF). When 8-methoxypsoralen (8-MOP) is used in PUVA therapy, it often produces intolerance reactions such as nausea, vomiting and headache. OBJECTIVES: To investigate whether 5-methoxypsoralen (5-MOP) is a safe and effective alternative to 8-MOP in PUVA therapy for MF. METHODS: A retrospective database search and chart review was done to identify patients with MF who received PUVA with either 5-MOP or 8-MOP as initial monotherapy at our institution. Between 1990 and 2004, 14 patients [seven men and seven women; mean age 70 years, range 51-82; National Cancer Institute disease stages IA (n = 6) and IB (n = 8)] received 5-MOP, and 24 patients [21 men and three women; mean age 58 years, range 28-89; disease stages IA (n = 11), IB (n = 12) and IIB (n = 1)] received 8-MOP. RESULTS: Twelve of 14 patients (86%) in the 5-MOP group and 22 of 24 (92%) in the 8-MOP group had a complete response to PUVA. These two subgroups of complete responders did not differ significantly in terms of PUVA therapy duration, number of treatments or cumulative UVA dose. They also did not differ significantly in terms of relapse-free rate [8% (one of 12) vs. 23% (five of 22)] or time to relapse [17 months (range 4-31) vs. 14 months (range 4-33)]. Moreover, PUVA maintenance therapy with either 5-MOP or 8-MOP in a subset of patients [26% (nine of 34)] did not affect long-term relapse-free status either. CONCLUSIONS: 5-MOP and 8-MOP have comparable therapeutic efficacy when used in PUVA therapy for MF.
5-Methoxypsoralen, in combination with UVA, is commonly used as a photochemotherapeutic agent for the treatment of psoriasis ... .
BACKGROUND: After oral intake, 5-methoxypsoralen (5-MOP) is as effective as 8-MOP for PUVA therapy for psoriasis, with a lower incidence of acute cutaneous side effects. OBJECTIVE: We compared bath-water delivery of 5-MOP and 8-MOP for photochemotherapy of psoriasis. METHODS: Twenty-two patients underwent phototesting with 0.0003% 5-MOP or 8-MOP aqueous solutions. Twelve patients with palmar psoriasis were studied with a side-to-side comparison, and 10 patients with recurrent plaque-type psoriasis were treated with one therapy or the other. RESULTS: Minimal phototoxic dose (MPD) values were 2.8 +/- 1.2 J/sq cm with 8-MOP and 2.0 +/- 1.2 J/sq cm with 5-MOP (p < 0.01). Both therapies cleared palmar lesions but 8-MOP required more UVA irradiation (46.3 +/- 21.0 J/sq cm vs 30.2 +/- 21.5 J/sq cm; p < 0.01) and more exposures (21.0 +/- 6.0 vs 17.0 +/- 5.0; p = 0.02). Bath-5-MOP-UVA was also more effective in the treatment of plaque-type psoriasis (cumulative UVA doses, 56.8 +/- 39.2 vs 59.1 +/- 27.9 J/sq cm; number of exposures, 20.0 +/- 5.7 vs 21.6 +/- 4.7), but these differences were not significant (p = NS). Patients developed an intense tan significantly earlier with 5-MOP than with 8-MOP (3.5 +/- 0.5 weeks vs 4.4 +/- 0.5 weeks; p < 0.01). CONCLUSION: Bath-5-MOP-UVA was more phototoxic than bath-8-MOP-UVA. It was more effective in the treatment of palmar psoriasis, whereas its greater pigmentogenic activity appeared to have an adverse effect on therapeutic effectiveness in the treatment of plaque-type psoriasis.
5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo. In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity. However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen. In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally. Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas. Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study. The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients. The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established. Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.

---

Drug Warnings
5-Methoxypsoralen has been reported to be the single active agent in berloque dermatitis, causing patchy hyperpigmentation of the face and neck ... .

C12H8O4

216.1895

216.042

484-20-8

Bergapten-d3;2749409-59-2

2355

White to off-white solid powder

1.4±0.1 g/cm3

412.4±45.0 °C at 760 mmHg

190-193 °C(lit.)

203.2±28.7 °C

0.0±1.0 mmHg at 25°C

1.635

2

0

4

1

16

325

0

BGEBZHIAGXMEMV-UHFFFAOYSA-N

InChI=1S/C12H8O4/c1-14-12-7-2-3-11(13)16-10(7)6-9-8(12)4-5-15-9/h2-6H,1H3

4-methoxyfuro[3,2-g]chromen-7-one

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 : ~20 mg/mL (~92.51 mM)
H2O : ~0.1 mg/mL (~0.46 mM)

Solubility in Formulation 1: 1 mg/mL (4.63 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

---

Solubility in Formulation 2: ≥ 1 mg/mL (4.63 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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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