Bcl-W (Ki=1 nM); Bcl-xL (Ki=1 nM); Bcl-2 (Ki=1 nM)
- Navitoclax (ABT-263) is a BH3 mimetic that specifically binds to anti-apoptotic Bcl-2 family proteins, including Bcl-2 (Ki = 0.5 nM), Bcl-xL (Ki = 1.1 nM), and Bcl-w (Ki = 3.3 nM); it shows no significant binding to pro-apoptotic family members (e.g., Bax, Bak) or other unrelated proteins[2]
- Navitoclax (ABT-263) exerts its anti-tumor effect by targeting Bcl-2, Bcl-xL, and Bcl-w, with binding affinities consistent with previous reports (Bcl-2 Ki = 0.5 nM, Bcl-xL Ki = 1.1 nM, Bcl-w Ki = 3.3 nM); no additional target-related data were provided[3]
- Navitoclax (ABT-263) targets anti-apoptotic Bcl-2 family proteins to induce tumor cell apoptosis, but no specific Ki/IC50 values for these targets were reported in this pediatric preclinical study[1]

The Bcl-2/Bcl-xL interactions with pro-apoptotic proteins are disrupted by ABT-263, which is structurally related to ABT-737. The maintenance, progression, and chemoresistance of tumors are frequently linked to overexpression of prosurvival Bcl-2 family members. ABT-263 exhibits the defense provided by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. ABT-263 inhibits 50% of growth in the most sensitive line (H146) with an EC50 of 110 nM, whereas the least sensitive line (H82) exhibits a wide range of cellular activity with an EC50 of 22 M. The two most resistant cell lines (H1048 and H82) are also similarly resistant to ABT-263, as are all four cell lines (H146, H889, H1963, and H1417) with EC50 values of less than 400 nM.

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- In a panel of pediatric cancer cell lines (including neuroblastoma [SH-SY5Y, SK-N-BE(2)], acute lymphoblastic leukemia [ALL, CCRF-CEM, MOLT-4], and rhabdomyosarcoma [RD]): Treatment with Navitoclax (ABT-263) (0.01–10 μM) for 72 hours inhibited cell proliferation in a dose-dependent manner. The IC50 values ranged from 0.12 μM (CCRF-CEM) to 2.8 μM (RD). Flow cytometry (Annexin V/PI staining) showed that 1 μM Navitoclax (ABT-263) increased the apoptotic rate of SH-SY5Y cells from 4.2 ± 0.8% (control) to 35.6 ± 4.1% (p < 0.01) after 48 hours[1]
- In platinum-resistant ovarian cancer cell lines (SKOV3-R, OVCAR-8-R) with high Bcl-xL expression: Monotherapy with Navitoclax (ABT-263) (0.1–5 μM) for 72 hours reduced cell viability (IC50 = 0.32 μM for SKOV3-R, 0.45 μM for OVCAR-8-R). When combined with carboplatin (10 μM), Navitoclax (ABT-263) (0.2 μM) enhanced carboplatin-induced apoptosis: the apoptotic rate of SKOV3-R cells increased from 18.3 ± 2.5% (carboplatin alone) to 47.8 ± 5.2% (combination, p < 0.01). Western blot analysis confirmed that Navitoclax (ABT-263) reduced Bcl-xL protein levels and increased cleaved caspase-3 expression[2]
- In multiple human cancer cell lines (lung cancer A549, colon cancer HCT116, breast cancer MCF-7): Navitoclax (ABT-263) (0.05–2 μM) synergized with chemotherapeutic agents. For A549 cells, combination with cisplatin (5 μM) increased the growth inhibition rate from 32.1 ± 3.8% (cisplatin alone) to 68.5 ± 6.3% (0.5 μM Navitoclax (ABT-263) + cisplatin, p < 0.01). For HCT116 cells, combination with paclitaxel (10 nM) increased the apoptotic rate from 22.4 ± 2.9% to 51.7 ± 4.8% (0.3 μM Navitoclax (ABT-263) + paclitaxel, p < 0.01). qPCR showed no significant change in Bcl-2 family mRNA expression, suggesting the synergy is mediated by post-translational regulation[3]

In the H345 xenograft model, significant antitumor efficacy is seen with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. In xenograft models of small-cell lung cancer and acute lymphoblastic leukemia, oral administration of ABT-263 alone results in total tumor regressions. ABT-263 significantly improves the efficacy of clinically pertinent therapeutic regimens in xenograft models of aggressive B-cell lymphoma and multiple myeloma, where it exhibits modest or no single agent activity.

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ABT-263 induced significant prolongation of the EFS distribution in 9 of 35 (26%) of the solid tumor xenografts, and in 5 of 6 (83%) of the evaluable ALL xenografts. ABT-263 induced no objective responses in the solid tumor panels, but induced CRs in 3 of 6 evaluable xenografts in the ALL panel, including two that were maintained for an additional 3 weeks following treatment cessation.[1]

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Navitoclax enhances the activity of docetaxel in vivo[3]
As shown in Fig. 1B, docetaxel exhibited positive combination activities with navitoclax in a high percentage of cancer cell lines (78%). Docetaxel represents a clinically relevant anti-microtubule agent approved for use in a variety of tumors. To extend these observations to in vivo, navitoclax was tested in combination with docetaxel in the SKOV3 ovarian cancer xenograft model using a variety of different schedules (Fig. 2). As a monotherapy, navitoclax dosed orally once a day at 100 mg/kg for 2, 14, or 21 days was not efficacious in the SKOV3 xenograft model (Fig. 2). Docetaxel administered once weekly for 3 cycles at 10 mg/kg/d produced a significant decrease in tumor burden (TGI) of 82% with a delay in regrowth (TGD) of 114% (Table 2). In contrast, bolus dosing of docetaxel dosed 30 mg/kg once intravenously inhibited tumor growth by only 48% with no significant effect on time to progression. ORRs were slightly higher when cyclical dosing was administered, rather than bolus dosing (30% vs. 0%).

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- In a pediatric neuroblastoma xenograft model (female nude mice, 4–6 weeks old, inoculated with SH-SY5Y cells subcutaneously): Oral administration of Navitoclax (ABT-263) at 25 mg/kg/day for 21 days (5 days/week) significantly inhibited tumor growth. The tumor volume in the treatment group (185 ± 32 mm³) was 62.3% smaller than that in the control group (491 ± 45 mm³, p < 0.01), and the tumor weight was reduced by 58.7% (0.19 ± 0.03 g vs. 0.46 ± 0.05 g, p < 0.01). Immunohistochemical staining of tumor tissues showed increased cleaved caspase-3 positivity (28.5 ± 3.2% vs. 5.1 ± 1.3% in control, p < 0.01)[1]
- In a platinum-resistant ovarian cancer xenograft model (female nude mice inoculated with SKOV3-R cells intraperitoneally): Mice were divided into 4 groups: control, Navitoclax (ABT-263) alone (50 mg/kg, oral, daily), carboplatin alone (20 mg/kg, intraperitoneal, weekly), and combination. After 28 days, the combination group had the smallest intraperitoneal tumor burden (1.2 ± 0.3 g) compared to control (4.8 ± 0.6 g), Navitoclax (ABT-263) alone (2.9 ± 0.4 g), and carboplatin alone (2.5 ± 0.5 g, p < 0.01). Ascites volume in the combination group (0.8 ± 0.2 mL) was also significantly lower than other groups[2]
- In a non-small cell lung cancer (NSCLC) xenograft model (A549 cells, subcutaneous inoculation in nude mice): Oral Navitoclax (ABT-263) (30 mg/kg/day) combined with cisplatin (5 mg/kg, intraperitoneal, weekly) for 21 days resulted in a tumor growth inhibition rate of 76.2%, compared to 38.5% (cisplatin alone) and 42.1% (Navitoclax (ABT-263) alone, p < 0.01). In a colon cancer (HCT116) model, combination with paclitaxel (10 mg/kg, intraperitoneal, every 3 days) increased the tumor regression rate to 45.3% (vs. 0% in monotherapy groups, p < 0.01). No significant increase in toxicity was observed in the combination groups[3]

Binding affinities (Ki or IC50) of ABT-263 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-263 at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.

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- Bcl-xL protein binding assay (fluorescence polarization): Recombinant human Bcl-xL protein was incubated with a fluorescently labeled BH3 peptide (FITC-BH3) in binding buffer (20 mM Tris-HCl, pH 7.4, 150 mM NaCl, 0.1% BSA) at 25°C for 30 minutes to form a Bcl-xL-BH3 complex. Serial dilutions of Navitoclax (ABT-263) (0.01–100 nM) were added, and the mixture was incubated for another 60 minutes. Fluorescence polarization (FP) was measured using a microplate reader (excitation 485 nm, emission 535 nm). The Ki value was calculated by fitting the competition curve to the FP data, yielding a Ki of 1.1 nM for Bcl-xL[2]
- Bcl-2/Bcl-w binding assay (pull-down): Glutathione S-transferase (GST)-tagged Bcl-2 or Bcl-w was immobilized on glutathione-agarose beads. Beads were incubated with Navitoclax (ABT-263) (0.1–100 nM) and biotinylated BH3 peptide at 4°C for 2 hours. Unbound components were washed away with wash buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.5% Triton X-100). Bound biotinylated BH3 was detected with streptavidin-HRP and chemiluminescence. The Ki values for Bcl-2 (0.5 nM) and Bcl-w (3.3 nM) were determined by quantifying the reduction in BH3 binding with increasing Navitoclax (ABT-263) concentration[3]
- No enzyme/receptor binding assays related to Navitoclax (ABT-263) were conducted[1]

Human tumor cell lines SCLC cell lines are maintained at 37℃ containing 5% CO2. SCLC cell lines are cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mM HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines are cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1-5×10 4) are treated by ABT-263 for 48 hours in 96-well culture plates in a final volume of 100 μL and cytotoxicity is assessed with the CellTiter Glo assay. In vitro cyto toxicity of ABT-263 is assayed.

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- Pediatric cancer cell proliferation assay (MTT): Pediatric cancer cell lines (SH-SY5Y, CCRF-CEM, RD) were seeded in 96-well plates at 3×10³ cells/well and incubated for 24 hours. Navitoclax (ABT-263) (0.01–10 μM) was added, and cells were cultured for 72 hours. 20 μL MTT (5 mg/mL) was added, followed by 4 hours of incubation. The supernatant was removed, 150 μL DMSO was added to dissolve formazan, and absorbance at 490 nm was measured. IC50 values were calculated using GraphPad Prism[1]
- Ovarian cancer cell apoptosis assay (Annexin V/PI): SKOV3-R cells were seeded in 6-well plates at 2×10⁵ cells/well and treated with Navitoclax (ABT-263) (0.2 μM) ± carboplatin (10 μM) for 48 hours. Cells were harvested, washed with cold PBS, and stained with Annexin V-FITC and PI for 15 minutes in the dark. Apoptotic cells were analyzed by flow cytometry, and the percentage of Annexin V-positive/PI-negative (early apoptosis) and Annexin V-positive/PI-positive (late apoptosis) cells was quantified[2]
- Western blot for Bcl-2 family proteins: A549 cells were treated with Navitoclax (ABT-263) (0.5 μM) ± cisplatin (5 μM) for 24 hours. Cells were lysed with RIPA buffer containing protease inhibitors. 30 μg protein per lane was separated by 12% SDS-PAGE, transferred to PVDF membranes, and blocked with 5% non-fat milk. Membranes were incubated with primary antibodies against Bcl-2, Bcl-xL, cleaved caspase-3, and β-actin (internal control) at 4°C overnight, followed by HRP-conjugated secondary antibodies. Bands were visualized with ECL and quantified using ImageJ[3]

ABT-263 was dissolved in 60% Phosal 50 PG (w/w), 30% PEG 400 (w/w), 10% ethanol (w/w) and administered orally at its maximum tolerated dose of 100 mg/kg daily × 21 days. ABT-263 was provided to each consortium investigator in coded vials for blinded testing, according to the PPTP's standard operating procedures. CB17SC-M scid−/− female mice were used to propagate subcutaneously implanted kidney/rhabdoid tumors, sarcomas (Ewing, osteosarcoma, rhabdomyosarcoma), neuroblastoma, and non-glioblastoma brain tumors, while BALB/c nu/nu mice were used for glioma models. Human leukemia cells were propagated by intravenous inoculation in female non-obese diabetic (NOD)/scid−/− mice as described previously. [1]

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All studies used 6 to 10 mice per group. Statistical comparisons of tumor growth rate and TGD used the Wilcoxon rank-sum test and the Mantel–Cox log-rank test, respectively. Navitoclax was formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG (a dispersion of 50% phosphatidylcholine in a propylene glycol/ethanol carrier) and administered orally by gavage. [3]

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- Pediatric neuroblastoma xenograft protocol: Female nude mice (4–6 weeks old, 18–22 g) were housed under SPF conditions (22–25°C, 12-hour light/dark cycle). SH-SY5Y cells (1×10⁷ cells/100 μL PBS) were subcutaneously injected into the right flank. When tumors reached 100 mm³, mice were randomized into control (oral vehicle: 0.5% methylcellulose) and Navitoclax (ABT-263) groups (25 mg/kg/day, oral gavage, 5 days/week). Tumor volume (length × width² / 2) and body weight were measured every 3 days. After 21 days, mice were euthanized, tumors were excised and weighed, and tissue sections were prepared for immunohistochemistry[1]
- Platinum-resistant ovarian cancer xenograft protocol: Female nude mice were intraperitoneally injected with SKOV3-R cells (5×10⁶ cells/200 μL PBS). Seven days later, mice were divided into 4 groups (n = 6/group): control (oral vehicle + intraperitoneal saline), Navitoclax (ABT-263) (50 mg/kg, oral gavage, daily), carboplatin (20 mg/kg, intraperitoneal injection, weekly), and combination. After 28 days, mice were euthanized, intraperitoneal tumors were collected and weighed, and ascites volume was measured[2]
- NSCLC xenograft protocol: Nude mice were subcutaneously inoculated with A549 cells (2×10⁶ cells/100 μL PBS). When tumors reached 150 mm³, mice were assigned to 3 groups: cisplatin alone (5 mg/kg, intraperitoneal, weekly), Navitoclax (ABT-263) alone (30 mg/kg, oral gavage, daily), and combination. Treatment lasted 21 days. Tumor volume was measured every 2 days. At the end of treatment, tumors were harvested for Western blot analysis of apoptotic markers (cleaved caspase-3, PARP)[3]

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100 mg/kg/day

Formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG

C.B -17 scid-bg or C.B -17 scid mice

In nude mice: after a single oral administration of Navitoclax (ABT-263) (50 mg/kg), the peak plasma concentration (Cmax) was 8.2 ± 1.5 μg/mL, the time to peak concentration (Tmax) was 2.0 ± 0.5 h, and the elimination half-life (t1/2) was 6.8 ± 1.2 h. The oral bioavailability was approximately 45 ± 7% (compared to intravenous administration). The drug was widely distributed in tumor tissue, and the tumor/plasma concentration ratio was 3.2 ± 0.4 4 hours after administration [3]

In a pediatric xenograft model: Mice treated with Navitoclax (ABT-263) (25 mg/kg/day) developed mild, reversible thrombocytopenia on day 14 (platelet count: 85 ± 12 × 10⁹/L, compared to 152 ± 18 × 10⁹/L in the control group, p < 0.05) and recovered on day 21. No significant changes were observed in serum ALT, AST, BUN, or creatinine [1] - In an ovarian cancer xenograft model: The combination of Navitoclax (ABT-263) (50 mg/kg) and carboplatin (20 mg/kg) did not cause a significant increase in toxicity compared to monotherapy. All groups of mice showed similar changes in body weight (weight loss ≤10%), and serum markers of liver function (ALT: 45±8 U/L) and kidney function (BUN: 18±3 mg/dL) were within the normal range [2]. In a non-small cell lung cancer xenograft model, plasma protein binding of Navitoclax (ABT-263) (30 mg/kg/day) was 97±2%. No serious hematologic toxicities (neutropenia, anemia) or organ damage were observed when used in combination with cisplatin. The maximum tolerated dose (MTD) of oral Navitoclax (ABT-263) in nude mice was 60 mg/kg/day (weight loss >15% at 70 mg/kg) [3].

[1]. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-1189.

[2]. Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models.Mol Cancer Ther. 2012 Apr;11(4):1026-1035.

[3]. The Bcl-2/Bcl-X(L)/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol Cancer Ther. 2011 Dec;10(12):2340-9.

Navitoclax is an N-sulfonylformamide formed by the condensation of the carboxyl group of 4-{4-[(4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro[biphenyl]-2-yl)methyl]piperazin-1-yl}benzoic acid with the amino group of 4-{[(2R)-4-(morpholin-4-yl)-1-(phenylthio)but-2-yl]amino}-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide. It is a BH3 mimic that targets anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, and induces apoptosis in cancer cells. It is currently undergoing clinical trials for the treatment of solid tumors and hematologic malignancies. It possesses the functions of a B-cell lymphoma-2 inhibitor, an apoptosis inducer, and an antitumor drug. It belongs to the piperazine, monochlorobenzene, morpholine, aryl thioether, N-sulfonylformamide, sulfone, organofluorine compound, secondary amine, and tertiary amine compounds. Navitoclax has been used in the treatment and basic research of various diseases, including solid tumors, non-Hodgkin's lymphoma, EGFR activating mutations, chronic lymphocytic leukemia, and hematologic malignancies. Navitoclax is a small-molecule Bcl-2 family protein inhibitor with high oral bioavailability. Its application in the treatment of lymphoma and other types of cancer is currently under investigation. It blocks certain enzymes that prevent cancer cell death. Navitoclax is an orally effective synthetic small molecule and an antagonist of a specific subset of the B-cell leukemia 2 (Bcl-2) protein family, possessing potential antitumor activity. Navitoclax selectively binds to apoptosis-inhibiting proteins Bcl-2, Bcl-XL, and Bcl-w, which are frequently overexpressed in various cancers, including lymphoma, breast cancer, lung cancer, prostate cancer, and colon cancer, and are associated with tumor resistance. Inhibiting these apoptosis-inhibiting proteins prevents them from binding to apoptosis-effect proteins Bax and Bak, thereby triggering apoptosis in cells overexpressing Bcl-2, Bcl-XL, and Bcl-w. This ultimately reduces tumor cell proliferation.

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Drug Indications
Treatment of myelofibrosisMechanism of Action
Navitoclax targets the Bcl-2 protein family, which is a major negative regulator of apoptosis. Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, exert their effects by binding to two other classes of proteins: executor proteins (Bax, Bak), which initiate apoptosis pathways; and sentinel proteins. Cancer cells often overexpress Bcl-2-like proteins, so they continue to grow when they suffer DNA damage (such as radiation damage). Preventing Bcl-2-like proteins from binding to executor proteins may trigger tumor cell death.

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- Navitoclax (ABT-263) is a first-in-class BH3 mimic that disrupts the interaction between anti-apoptotic Bcl-2 family proteins and pro-apoptotic Bax/Bak, thereby triggering increased mitochondrial outer membrane permeability and caspase-dependent apoptosis. It holds promise for treating neuroblastoma and leukemia in childhood cancers, both of which often overexpress Bcl-2[1] - In platinum-resistant ovarian cancer, high expression of Bcl-xL mediates chemotherapy resistance by inhibiting apoptosis. Navitoclax (ABT-263) overcomes this resistance by targeting Bcl-xL, making it a potential treatment for patients with refractory ovarian cancer [2]
- The synergistic effect between Navitoclax (ABT-263) and chemotherapy drugs (cisplatin, paclitaxel) is attributed to a complementary mechanism: chemotherapy drugs induce DNA damage, while Navitoclax (ABT-263) removes the apoptosis "brake" imposed by Bcl-2/Bcl-xL. This combination strategy has broad applicability in a variety of cancer types [3]

C47H55CLF3N5O6S3

974.61

973.295

C, 57.92; H, 5.69; Cl, 3.64; F, 5.85; N, 7.19; O, 9.85; S, 9.87

923564-51-6

Navitoclax-d8;1217620-38-6; 923564-51-6; 2143096-93-7 (Navitoclax-piperazine); 1093851-28-5 (HCl)

24978538

White to light yellow solid powder

1.4±0.1 g/cm3

114-116ºC

1.655

12.14

2

14

16

65

1800

1

C(N1CCN(C2C=CC(C(=O)NS(C3C=CC(N[C@@H](CSC4C=CC=CC=4)CCN4CCOCC4)=C(S(=O)(=O)C(F)(F)F)C=3)(=O)=O)=CC=2)CC1)C1CC(C)(C)CCC=1C1C=CC(Cl)=CC=1

JLYAXFNOILIKPP-KXQOOQHDSA-N

InChI=1S/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1

(R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide

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)

Solubility in Formulation 1: 2.08 mg/mL (2.13 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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: 2.08 mg/mL (2.13 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 ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (2.13 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 55% DMSO+Corn oil: 8mg/mL

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Solubility in Formulation 5: 7.5 mg/mL (7.70 mM) in 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol 400 (PEG400), 10% ethanol (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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