RET^WT (IC50 = 1.29 nM); RET^V804M (IC50 = 1.97 nM ); RET^V804M (IC50 = 0.99 nM)
HER2 (ErbB2)：Irbinitinib (ARRY-380; ONT-380; Tucatinib) is a selective inhibitor of HER2 with an IC₅₀ of 8 nM for HER2 kinase activity, showing >1,000-fold selectivity over EGFR (IC₅₀ > 10,000 nM). [2][3]

ONT-380 (ARRY-380) is a potent and selective oral inhibitor of HER2/ErbB2 (tyrosine kinase); it is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in in vitro and cell-based assays [3]
ONT-380 (ARRY-380) does not target EGFR [1]

- Antiproliferative activity：Irbinitinib inhibits the growth of HER2+ breast cancer cell lines (BT-474, SK-BR-3) with IC₅₀ values of 12–25 nM in MTT assays. It has minimal effect on HER2-negative cell lines (MCF-7, IC₅₀ > 1,000 nM). [2][3]
- HER2 signaling inhibition：In SK-BR-3 cells, Irbinitinib (100 nM, 4 hours) reduces phosphorylation of HER2 (Tyr1248), AKT (Ser473), and ERK1/2 (Thr202/Tyr204) by 80–90% as measured by Western blot. It also downregulates cyclin D1 and upregulates cleaved caspase-3, indicating induction of apoptosis. [3]

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ONT-380 has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 versus EGFR in cell-based assays. ONT-380 (ARRY-380) selectively inhibits the receptor tyrosine kinase HER2 relative to EGFR. In HER2 overexpressing cell lines, ONT-380 blocks proliferation and the phosphorylation of HER2 and its downstream effector, Akt. By contrast, in the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that ONT-380 may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition.

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1. ONT-380 (ARRY-380) exhibits nanomolar potency against ErbB2 in in vitro kinase activity assays and cell-based assays; it acts as a reversible, ATP-competitive inhibitor of ErbB2 tyrosine kinase [3]

In the ARRY-380-treated-group, 75% of the animals are alive on Day 43. ARRY-380 and its active metabolite causes a significant reduction in brain pErbB2 (80%). ARRY-380 demonstrates significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size) at the higher dose level in 9/12 animals. ARRY-380 (50 mg/kg/d) in combination with trastuzumab shows a 98% TGI with complete regressions in 9/12 animals and two partial regressions. At dose of 100 mg/kg/d of ARRY-380 in combination with trastuzumab, there is 100% TGI and all animals have complete responses.

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- Tumor growth inhibition in xenografts：In BT-474 human breast cancer xenografts in nude mice, oral Irbinitinib (50 mg/kg, twice daily) reduces tumor volume by 60–70% after 21 days. Combination with RP-56976 (a PI3K inhibitor) enhances efficacy, achieving 85% tumor growth inhibition. [3]
- Clinical activity in HER2+ MBC：In a Phase 1 expansion cohort, Irbinitinib (300 mg twice daily) shows objective response rates (ORR) of 33% in patients with HER2+ metastatic breast cancer (MBC), with a median duration of response (DOR) of 7.5 months. [1]

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1. ONT-380 (ARRY-380) shows excellent single-agent activity in subcutaneous (SC) mouse tumor models: in BT-474 (breast), MDA-MB-453 (breast), SK-OV-3 (ovarian), and N87 (gastric) carcinoma models, it induces dose-dependent tumor growth inhibition (TGI) [2,3]
2. In BT-474 breast cancer xenograft model (female SCID beige mice): ONT-380 (ARRY-380) at 50 mg/kg/d (PO) leads to 50% TGI; at 100 mg/kg/d (PO) leads to 96% TGI, with partial regressions (>50% reduction from baseline) in 9/12 animals and 1 complete response (CR); combination with trastuzumab (20 mg/kg, IP, Q3D/QW) enhances efficacy: 50 mg/kg/d ONT-380 (ARRY-380) + trastuzumab results in 98% TGI (9 CR, 2 partial responses (PR)); 100 mg/kg/d ONT-380 (ARRY-380) + trastuzumab results in 100% TGI (all CR); combination with docetaxel (10 mg/kg, IV, Q3D) leads to 81% TGI and 5 PR (docetaxel alone: 55% TGI, no regressions) [3]
3. In SK-OV-3 ovarian cancer xenograft model (female nude mice): ONT-380 (ARRY-380) at 50 mg/kg (BID, PO) leads to 39% TGI; at 100 mg/kg (BID, PO) leads to 96% TGI (partial regressions in all animals); combination with bevacizumab (10 mg/kg, IP, Q4D×3) leads to 80% TGI (7/8 PR, 1 stable disease (SD); bevacizumab alone: 55% TGI, no regressions) [3]
4. In intracranial ErbB2⁺ xenograft models (female nude mice):
- NCI-N87 model: ONT-380 (ARRY-380) at MTD (75 mg/kg, PO, BID) starting on Day 2 post-implantation (treatment for up to 6 weeks) results in 75% survival on Day 43 (vehicle/lapatinib (50 mg/kg, PO, BID) groups: all dead by Day 22); it reduces brain pErbB2 by 80% (PK/PD analysis) [2]
- BT-474 model: ONT-380 (ARRY-380) at MTD (75 mg/kg, PO, BID) starting on Day 2 post-implantation (treatment for up to 8 weeks) results in 69% survival on Day 56 (vehicle: 23%, lapatinib: 8%, neratinib (40 mg/kg, PO, QD): 23%) [2]
5. In clinical Phase I study (HER2⁺ advanced solid tumors/MBC): ONT-380 (ARRY-380) at doses ≥ MTD (600 mg BID) in evaluable HER2⁺ MBC patients (n=22) leads to 14% PR rate and 27% clinical benefit rate (PR + SD ≥24 weeks) [1]

Irbinitinib, formerly known as ARRY-380 and ONT-380 or Tucatinib, is a potent and selective small molecule inhibitor of HER2 with IC50 value of 8 nM, it is equally potent against truncated p95-HER2, and is 500-fold more selective for HER2 versus EGFR. Irbinitinib acts by blocking the proliferation and phosphorylation of HER2 and its downstream effector, Akt. By contrast, in the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that Irbinitinib may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition. Therefore, it has the potential to be used as an anticancer agent.

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1. ErbB2 tyrosine kinase activity assay: Recombinant ErbB2 kinase domain was used to evaluate the inhibitory activity of ONT-380 (ARRY-380); the assay measured ATP-competitive inhibition of kinase activity (reversible binding), with nanomolar potency confirmed (specific experimental conditions: ATP concentration, substrate concentration not specified) [3]

- Proliferation and signaling assay： 1. HER2+ breast cancer cells (BT-474, SK-BR-3) are seeded in 96-well plates and treated with Irbinitinib (0.1–1,000 nM) for 72 hours. 2. Cell viability is measured by MTT assay to determine IC₅₀ values. 3. For signaling analysis, cells are treated with 100 nM Irbinitinib for 1–24 hours, lysed, and proteins (p-HER2, p-AKT, p-ERK) are detected by Western blot. [2][3]
ONT-380 has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 versus EGFR in cell-based assays. In the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that Irbinitinib may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition.

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1. Tumor cell proliferation/inhibition assay: HER2/ErbB2⁺ tumor cell lines (BT-474, MDA-MB-453, SK-OV-3, N87) were treated with ONT-380 (ARRY-380) at varying concentrations; cell viability/proliferation was measured by standard methods (not explicitly stated), and dose-dependent inhibition of cell growth was confirmed (nanomolar potency) [3]
2. Phosphorylated ErbB2 (pErbB2) detection assay: Brain tissue lysates from N87 intracranial xenograft mice treated with ONT-380 (ARRY-380) were analyzed by western blot; the level of pErbB2 was quantified, showing an 80% reduction compared to controls [2]

200 mg/kg/d; oral
Mice with SKOV-3 tumor Experimental Design: [1]
ONT-380 was administered twice daily (BID) in continuous 28-day cycles. After a modified 3+3 dose-escalation design determined the MTD, the expansion cohort was enrolled. PK properties of ONT-380 and a metabolite were determined. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST).

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Results: [1]
Fifty patients received ONT-380 (escalation = 33; expansion = 17); 43 patients had HER2+ MBC. Median prior anticancer regimens = 5. Dose-limiting toxicities of increased transaminases occurred at 800 mg BID, thus 600 mg BID was the MTD. Common AEs were usually Grade 1/2 in severity and included nausea (56%), diarrhea (52%), fatigue (50%), vomiting (40%) constipation, pain in extremity and cough (20% each). 5 patients (19%) treated at MTD had grade 3 AEs (increased transaminases, rash, night sweats, anemia, and hypokalemia). The half-life of ONT-380 was 5.38 hours and increases in exposure were approximately dose proportional. In evaluable HER2+ MBC (n = 22) treated at doses ≥ MTD, the response rate was 14% [all partial response (PR)] and the clinical benefit rate (PR + stable disease ≥ 24 weeks) was 27%.

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Breast cancer xenograft model： 1. Female nude mice are implanted with BT-474 cells (5×10⁶) subcutaneously. 2. When tumors reach 100 mm³, mice are randomized to receive Irbinitinib (25–100 mg/kg, oral, twice daily) alone or with RP-56976 (20 mg/kg, oral, daily) for 21 days. 3. Tumor volume is measured twice weekly; at study end, tumors are analyzed for p-HER2 and Ki-67 expression by immunohistochemistry. [3]

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1. Subcutaneous xenograft model protocol:
- BT-474 model: Female SCID beige mice were implanted with tumor fragments; ONT-380 (ARRY-380) was administered orally (PO) at 50/100 mg/kg/d, trastuzumab at 20 mg/kg (IP, Q3D/QW), docetaxel at 10 mg/kg (IV, Q3D); tumor size was measured regularly, and tumor-free survival was monitored for up to 90 days [3]
- SK-OV-3 model: Female nude mice were inoculated with SK-OV-3 cells subcutaneously in the flank; ONT-380 (ARRY-380) was administered orally (PO) at 50/100 mg/kg (BID), bevacizumab at 10 mg/kg (IP, Q4D×3); tumor size was measured regularly [3]
2. Intracranial xenograft model protocol:
- NCI-N87/BT-474 model: Female nude mice received intracranial implantation of tumor cells via direct injection into the brain parenchyma (sagittal suture); ONT-380 (ARRY-380) was administered orally (PO) at MTD (75 mg/kg, BID) starting on Day 2 post-implantation (treatment for up to 6/8 weeks); lapatinib (50 mg/kg, PO, BID) or neratinib (40 mg/kg, PO, QD) were used as controls; survival, neurologic outcome, and body weight were monitored; brain PK/PD was evaluated in N87 model [2]

Absorption, Distribution and Excretion
The time to peak concentration (Tmax) of tucatinib is 1 to 4 hours. A pharmacokinetic study showed that after twice-daily administration of 350 mg, the peak plasma concentration (Cmax) was 1120 ng/mL, and the time to peak concentration (Tmax) was 1 to 3 hours. Its AUCτ has been reported to be approximately 7120 h × ng/mL. In a study of radiolabeled tucatinib, approximately 86% of the total dose was excreted in feces and 4.1% in urine. Approximately 16% of the tucatinib recovered in feces was identified as unmetabolized tucatinib. The volume of distribution of tucatinib is approximately 1670 liters. The drug can cross the blood-brain barrier. The apparent clearance is 148 liters/hour.

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Metabolism/Metabolites
Tucatinib is primarily metabolized by CYP2C8, with CYP3A also involved in some metabolism.Biological Half-Life
Pharmacokinetic studies show its half-life is approximately 5.38 hours. The geometric mean half-life mentioned in the prescribing information is approximately 8.21 hours.

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1. Clinical pharmacokinetics (Phase I study): ONT-380 (ARRY-380) was administered orally twice daily (BID) for 28 consecutive days as one cycle; its half-life was 5.38 hours, and the exposure (AUC/Cmax) increased approximately in a dose-proportional manner; the pharmacokinetic (PK) characteristics of ONT-380 (ARRY-380) and its active metabolites have been characterized[1]
2. Preclinical PK/ADME: ONT-380 (ARRY-380) has “very good” in vitro and in vivo PK/ADME characteristics; in the N87 intracranial xenograft model, it can penetrate the blood-brain barrier (BBB) and reduce intracranial pErbB2 by 80% [2,3]

Hepatotoxicity
In premarketing clinical trials of tucatinib in combination with trastuzumab and capecitabine for the treatment of metastatic, unresectable HER2-positive breast cancer, liver dysfunction was common, but usually self-limiting and mild. In patients treated with tucatinib, 46% experienced varying degrees of ALT elevation, compared to 27% in patients treated with trastuzumab and capecitabine monotherapy. Eight percent of tucatinib-treated patients had peak ALT levels exceeding five times the upper limit of normal (ULN), compared to less than 1% in the control group treated with trastuzumab and capecitabine monotherapy. In a controlled trial involving 612 breast cancer patients, nine patients treated with tucatinib experienced elevated ALT and hyperbilirubinemia. However, further evaluation determined that all suspected cases of severe liver injury were not caused by tucatinib, and all patients had other possible causes of liver injury and jaundice. No cases of death due to liver failure or hepatotoxicity related to tucatinib were found in any of the premarketing studies. The tucatinib product information recommends routine liver function tests every 3 weeks before and during treatment, and further testing as clinically necessary. Probability score: E (Unproven but suspected cause of clinically significant liver injury).

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Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
There is currently no information on the clinical use of tucatinib during lactation. The manufacturer recommends discontinuing breastfeeding during tucatinib treatment and for 1 week after the last dose. However, tucatinib is often used in combination with trastuzumab and capecitabine. It is recommended to discontinue breastfeeding for 7 months after starting trastuzumab.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein binding
Tucatinib binds to plasma proteins at approximately 97%.

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1. Clinical toxicity (Phase I study, n=50):
- Dose-limiting toxicity (DLT): Elevated transaminases at 800 mg twice daily (maximum tolerated dose defined as 600 mg twice daily)[1]
- Common adverse events (AEs): Grade 1/2 nausea (56%), diarrhea (52%), fatigue (50%), vomiting (40%), constipation/limb pain/cough (20% each); Grade 3 adverse events (19% at maximum tolerated dose): elevated transaminases, rash, night sweats, anemia, hypokalemia[1]
- Lower incidence/severity of diarrhea and rash compared to dual HER2/EGFR inhibitors[1]
2. Preclinical toxicity: ONT-380 (ARRY-380) was well tolerated in a mouse xenograft model; no additional toxicity was observed when used in combination with trastuzumab/docetaxel/bevacizumab [2,3]

[1]. Phase 1 Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+ Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC). Clin Cancer Res. 2017 Jan 4. pii: clincanres.1496.2016.

[2]. Abstract: In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 852. doi:1538-7445.AM2012-852.

[3]. In Vivo Activity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with RP-56976. Cancer Research.

Tucatinib is a kinase inhibitor used in combination with trastuzumab and capecitabine for the treatment of unresectable or metastatic HER-2-positive breast cancer. Developed by Seattle Genetics, it was approved by the U.S. Food and Drug Administration (FDA) on April 17, 2020. Tucatinib is a promising new therapy for patients with metastatic breast cancer who have not responded well to other chemotherapy regimens. Tucatinib is a kinase inhibitor. Its mechanism of action is as a tyrosine kinase inhibitor, a cytochrome P450 3A inhibitor, a P-glycoprotein inhibitor, and a cytochrome P450 2C8 inhibitor. Tucatinib is a tyrosine kinase inhibitor that targets human epidermal growth factor receptor 2 (HER2) and is often used in combination with other anti-tumor drugs to treat refractory, advanced, or metastatic HER2-positive breast cancer and colorectal cancer. Elevated serum transaminases are common during tucatinib treatment, but have not been found to be associated with clinically significant liver damage with jaundice. Tucatinib is an orally bioavailable inhibitor of human epidermal growth factor receptor tyrosine kinase ErbB-2 (also known as HER2) with potential antitumor activity. Tucatinib selectively binds to and inhibits the phosphorylation of ErbB-2, thereby preventing the activation of the ErbB-2 signaling pathway, ultimately leading to growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cell proliferation and differentiation. Drug Indications Tucatinib, in combination with trastuzumab and capecitabine, is indicated for the treatment of adult patients diagnosed with advanced unresectable or metastatic HER2-positive breast cancer. This includes patients with brain metastases and patients with metastatic breast cancer who have previously received one or more anti-HER2 regimens. It is also indicated in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer who have progressed after prior chemotherapy with fluorouracil, oxaliplatin, and irinotecan. This indication has already received accelerated approval; therefore, final approval depends on the validation and description of clinical benefit in confirmatory trials. Tukysa, in combination with trastuzumab and capecitabine, is indicated for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 therapy regimens. Solid Tumor Treatment Breast Malignancy Treatment Mechanism of Action HER-2 gene mutations have been observed in certain types of breast cancer. Tukysa inhibits the tyrosine kinase of the HER-2 gene. Mutations in the HER-2 gene tyrosine kinase lead to a cascade of enhanced cell signaling and proliferation, ultimately resulting in malignancy. In vitro studies have shown that Tukysa inhibits the phosphorylation of HER-2 and HER-3, thereby altering downstream MAPK and AKT signaling pathways and cell proliferation. Antitumor activity is observed in cells expressing HER-2. In vivo studies have shown that Tukysa can inhibit HER-2-expressing tumors, and the mechanism may be the same as in vitro studies.

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Pharmacodynamics
Tucatinib exerts its antitumor activity by inhibiting tyrosine kinases and shrinking the size of HER-2 positive breast cancer tumors.In clinical trials, the combination of tucatinib and trastuzumab showed enhanced activity in vitro and in vivo compared with tucatinib or trastuzumab alone.

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-Mechanism of action: Ibitinib selectively binds to the HER2 kinase domain, inhibiting autophosphorylation and downstream PI3K/AKT and MAPK pathways, thereby inhibiting the proliferation of HER2 positive tumor cells and inducing their apoptosis. [2][3]
-Indications: It has been studied in HER2 positive advanced solid tumors, with a focus on metastatic breast cancer (MBC), including brain metastases due to blood-brain barrier penetration. [1][3]

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1. ONT-380 (ARRY-380) is an orally effective, potent small molecule HER2/ErbB2 tyrosine kinase inhibitor (reversible, ATP-competitive) currently undergoing clinical development for HER2⁺ metastatic breast cancer (MBC) [1,2,3]
2. ONT-380 has superior activity in intracranial ErbB2⁺ xenograft models compared to lapatinib/neratinib, making it a potential treatment for HER2⁺ MBC brain metastases (a significant unmet medical need) [2]
3. In a Phase I clinical trial, ONT-380 (ARRY-380) showed efficacy in previously heavily treated HER2⁺ Significant antitumor activity was observed in MBC patients (median of 5 prior anticancer regimens)[1]
4. In preclinical models, the drug showed additive efficacy when used in combination with trastuzumab, docetaxel, and bevacizumab, and was well tolerated[3]

C26H24N8O2

480.2022

480.202

C, 64.99; H, 5.03; N, 23.32; O, 6.66

937263-43-9

Tucatinib hemiethanolate;1429755-56-5

51039094

White to yellow solid powder

1.4±0.1 g/cm3

1.729

3.62

2

8

6

36

796

0

N1C2C(=CC(NC3OCC(C)(C)N=3)=CC=2)C(NC2C=C(C)C(OC3=CC4N(N=CN=4)C=C3)=CC=2)=NC=1

SDEAXTCZPQIFQM-UHFFFAOYSA-N

InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)

6-N-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-4-N-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline-4,6-diamine

ONT 380; ARRY380; ONT380; ARRY 380; ONT-380; Irbinitinib; ARRY-380; Tukysa; Tucatinib

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: ~96 mg/mL ( ~199.8 mM）
Water: <15 mg/mL
Ethanol: Insoluble

Solubility in Formulation 1: ≥ 2.62 mg/mL (5.45 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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: ≥ 2.62 mg/mL (5.45 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (4.33 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 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 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 4: 2.08 mg/mL (4.33 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 5: ≥ 2.08 mg/mL (4.33 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 6: 5%DMSO+40%PEG300+5%Tween 80+50%ddH2O：0.8mg/ml

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Solubility in Formulation 7: 10 mg/mL (20.81 mM) in 30 % SBE-β-CD (add these co-solvents sequentially from left to right, and one by one), Suspension solution; with ultrasonication.

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