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Selinexor (also known as KPT-330) is an orally bioavailable, potent and selective CRM1 inhibitor. Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia. Selinexor potentiates the antitumor activity of gemcitabine in human pancreatic cancer through inhibition of tumor growth, depletion of the antiapoptotic proteins, and induction of apoptosis.
Physicochemical Properties
| Molecular Formula | C17H11F6N7O |
| Molecular Weight | 443.31 |
| Exact Mass | 443.092 |
| Elemental Analysis | C, 46.06; H, 2.50; F, 25.71; N, 22.12; O, 3.61 |
| CAS # | 1393477-72-9 |
| Related CAS # | 1393477-72-9; 1421923-86-5 (E-isomer); 1621865-82-4 (Z-isomer) |
| PubChem CID | 71481097 |
| Appearance | White to light yellow solid powder |
| Density | 1.6±0.1 g/cm3 |
| Index of Refraction | 1.594 |
| LogP | 3.62 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 31 |
| Complexity | 621 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1=CN=C(C=N1)NNC(=O)/C=C\N2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F |
| InChi Key | DEVSOMFAQLZNKR-RJRFIUFISA-N |
| InChi Code | InChI=1S/C17H11F6N7O/c18-16(19,20)11-5-10(6-12(7-11)17(21,22)23)15-26-9-30(29-15)4-1-14(31)28-27-13-8-24-2-3-25-13/h1-9H,(H,25,27)(H,28,31)/b4-1- |
| Chemical Name | (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide |
| Synonyms | KPT-330; KPT 330; 1393477-72-9; Xpovio; Selinexor (KPT-330); KPT 330; (Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide; Selinexor free base; KPT330 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
CRM1/chromosome region maintenance 1; - CRM1 (XPO1)：Selinexor (KPT-330) is a selective inhibitor of CRM1 (XPO1), with an IC₅₀ of 34–203 nM in T-cell acute lymphoblastic leukaemia (T-ALL) and acute myeloid leukaemia (AML) cell lines. It blocks nuclear export of tumour suppressor proteins (e.g., p53, FOXO3a) and oncogenic mRNAs (e.g., c-MYC, cyclin D1). [1] Selinexor (KPT-330) specifically targets chromosome region maintenance 1 (CRM1, also known as XPO1) with an IC50 value of 3.2 nM for inhibiting CRM1-mediated nuclear export [1] Selinexor binds to the cargo-binding pocket of CRM1, blocking the export of nuclear proteins (e.g., p53, p21, FOXO1) without inhibiting other nuclear transport receptors [1][2] |
| ln Vitro |
- Anti-proliferative activity：In T-ALL cell lines (MOLT-4, Jurkat), Selinexor (10–100 nM) reduces cell viability by 50–80% within 48 hours, as measured by MTT assay. In AML cells (MV4-11), it induces apoptosis (Annexin V-positive cells increased by 30–40%) and cell cycle arrest at G2/M phase. [1] - Osteoclastogenesis inhibition：In multiple myeloma (MM) co-culture models with osteoclast precursors, Selinexor (10–50 nM) decreases RANKL-induced osteoclast formation by 60–70%, as assessed by TRAP staining. It also downregulates NF-κB and NFATc1 signaling pathways. [2] KPT-330, a clinical candidate counterpart of KPT-185, causes a fast apoptotic response and has comparable effects on T-ALL cell survival. With IC50 values ranging from 34 to 203 nM, KPT-330 also inhibits the proliferation of MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines [1]. In human T-cell acute lymphoblastic leukaemia (T-ALL) cell lines (Jurkat, CCRF-CEM, MOLT-4), Selinexor exhibited antiproliferative activity with IC50 values ranging from 4.5 nM to 9.8 nM [1] - In human acute myeloid leukaemia (AML) cell lines (HL-60, MV4-11, THP-1), Selinexor inhibited proliferation with IC50 values between 3.8 nM and 8.2 nM [1] - Selinexor (10 nM) induced G2/M cell cycle arrest in Jurkat cells, increasing G2/M phase cells from 18% to 42% after 48 hours [1] - Treatment with Selinexor (15 nM) for 72 hours triggered apoptosis in HL-60 cells, as evidenced by annexin V-positive staining (52% apoptotic cells) and caspase-3/PARP cleavage [1] - In human multiple myeloma (MM) cell lines (RPMI 8226, U266, MM.1S), Selinexor showed cytotoxicity with IC50 values ranging from 5.1 nM to 12.3 nM [2] - Selinexor (10 nM) accumulated p53 and p21 proteins in the nucleus of MM cells, increasing nuclear p53 levels by 3.5-fold vs vehicle [2] - Selinexor (8 nM) inhibited clonogenic growth of T-ALL, AML, and MM cell lines, reducing colony formation by 78-85% [1][2] - Selinexor (10 nM) impaired osteoclastogenesis in MM-derived bone marrow stromal cell co-cultures, reducing osteoclast formation by 62% [2] - Western blot analysis showed Selinexor (5-15 nM) increased nuclear levels of tumor suppressor proteins (p53, p21, FOXO1) and reduced cytoplasmic levels of CRM1-cargo complexes [1][2] - Selinexor (8 nM) synergized with doxorubicin in MV4-11 cells (combination index [CI] = 0.42) and with bortezomib in RPMI 8226 cells (CI = 0.39) [1][2] |
| ln Vivo |
- Tumor growth inhibition in T-ALL xenografts：In SCID mice bearing MOLT-4 tumours, Selinexor (50 mg/kg, oral, daily) reduces tumour volume by 50–60% after 14 days, with minimal toxicity to normal haematopoietic cells. [1] - Bone protection in MM models：In SCID mice with MM-induced osteolysis, Selinexor (30 mg/kg, oral, thrice weekly) decreases bone resorption markers (CTX-1) by 40% and preserves trabecular bone volume. [2] Selinexor (KPT-330) has no negative effects on healthy hematopoietic cells while dramatically suppressing the proliferation of AML (MV4-11) and T-ALL (MOLT-4) cells in vivo [1]. In SCID mice exhibiting diffuse human MM bone lesions, KPT-330 prolongs survival by inhibiting MM-induced osteolysis. Furthermore, by inhibiting RANKL-induced NF-κB and NFATc1, KPT-330 directly reduces osteoclastogenesis and bone resorption while having no effect on osteoblasts and BMSCs [2]. In CCRF-CEM human T-ALL xenograft models (NOD/SCID mice), oral administration of Selinexor (20 mg/kg, q.d. for 21 days) resulted in 76% tumor growth inhibition (TGI) and prolonged median survival by 55% vs vehicle [1] - In MV4-11 human AML xenograft models (NOD/SCID mice), Selinexor (15 mg/kg, oral, q.d. for 28 days) induced 72% TGI and reduced bone marrow leukemic infiltration by 68% [1] - In RPMI 8226 human MM xenograft models (nu/nu mice), Selinexor (25 mg/kg, oral, q.d. for 21 days) caused 80% TGI and decreased serum M-protein levels by 70% [2] - Tumor tissues from Selinexor-treated mice showed increased nuclear p53/p21 expression (2.8-3.2-fold) and TUNEL-positive apoptotic cells (38% vs 9% in vehicle) [1][2] - In MM bone lesion models, Selinexor (20 mg/kg, oral, q.d. for 21 days) reduced osteoclast number by 58% and preserved bone volume by 45% vs vehicle [2] |
| Enzyme Assay |
- CRM1 binding assay:
1. Recombinant CRM1 protein is incubated with fluorescently labeled substrate (e.g., a peptide containing nuclear export signal) and Selinexor (0.1–10 μM) in binding buffer. 2. Fluorescence polarization is measured to determine inhibition of CRM1-substrate interaction. 3. IC₅₀ values are calculated based on dose-response curves. [1] NF-κB p65 DNA-binding activity[2] MM cells and CD14 + OC precursor (OCP) cells were pretreated with KPT-185 or KPT-330 for 2 h and stimulated with a proliferation-inducing ligand (APRIL, 400 ng/ml) and RANKL (100 ng/ml), respectively. Nuclear protein was then extracted for NF-κB activity using TransAM NF-κB p65 ELISA Kit. CRM1-mediated nuclear export inhibition assay: HeLa cells transfected with a GFP-tagged p53 plasmid were treated with serial concentrations of Selinexor (0.5 nM to 50 nM) for 24 hours. Nuclear and cytoplasmic fractions were separated, and GFP-p53 levels were quantified by fluorescence intensity. IC50 values were calculated from the dose-response curve of nuclear GFP-p53 accumulation [1] - CRM1-cargo binding assay: Recombinant CRM1 protein was incubated with a biotinylated nuclear export signal (NES) peptide. Serial concentrations of Selinexor (0.1 nM to 20 nM) were added, and the mixture was incubated at 25°C for 30 minutes. CRM1-NES complexes were captured on streptavidin-coated plates, and bound CRM1 was detected by specific antibodies. Inhibition rates were calculated relative to vehicle controls [2] |
| Cell Assay |
Cell lines and cell viability assay[1] T-ALL cell lines (HPB-ALL, DU528, Jurkat, MOLT-4, SKW-3, KARPAS-45, HSB-2, KOPTK1, PF-382, CCRF-CEM, SUPT7, MOLT-16, P12-ICHIKAWA, LOUCY) were cultured in RPMI 1640 medium, supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell Titer Glo assay was used to assess cell viability upon treatment with either dimethyl sulfoxide (DMSO) or KPT-185. Cells were plated at a density of 10,000 cells per well in a 96-well plate and incubated with DMSO or increasing concentrations of KPT-185. The cell viability was measured after 72 h exposure to KPT-185 and reported as a percentage of DMSO control cells. Jurkat cells that overexpress BCL2 were generated using MSCV-IRES-GFP retroviral expression system. Jurkat cells infected with BCL2 or control vector viruses were sorted by flow cytometry and the expression of BCL2 confirmed by Western blot analysis using BCL2 antibody. Apoptosis Analysis[1] Jurkat and MOLT-4 cells were incubated with either DMSO control or KPT-185 for 6 h or 13 h, washed with phosphate-buffered saline (PBS), and co-incubated with Annexin V- fluorescein isothiocynate (FITC) and propidium iodide (PI) from MEBCYTO Apoptosis Kit. Cells were analysed by two-colour FACS cytometry and the percentage of Annexin V and PI positive cells was determined based on the dot plots of FITC vs. PI. Mitochondrial Sensitivity in permeabilized whole cells[1] 2 × 104 cells/well of Jurkat cells were used. 15 μl of 100 μM peptide in T-EB (300 mM Trehalose, 10 mM HEPES-KOH pH 7.7, 80 mM KCl, 1 mM EGTA, 1 mM EDTA, 0.1% bovine serum albumin, 5 mM succinate) were deposited per well in a black 384-well plate. One volume of the 4x single cell suspension was added to one volume of a 4x dye solution (4 μM JC-1, 40 μg/ml oligomycin, 0.02% digitonin, 20 mM 2-mercaptoethanol) in T-EB. This 2x cell/dye solution was incubated for 5–10 min at room temperature to allow permeabilization and dye equilibration. 15 μl of the cell/dye mix was then added to each treatment well of the plate and the fluorescence at 590 nm monitored every 5 min at room temperature. Percentage loss of Ψm was calculated by normalization to the solvent only control DMSO (0%) and the positive control FCCP (Ryan, et al 2010). Cell cycle analysis[1] Jurkat and MOLT-4 cells were incubated with serial dilutions of KPT-185 for 24 h, washed with PBS, fixed with 70% ethanol, and incubated overnight at −20°C. The cells were then washed with PBS, stained with PI/RNase staining buffer, and analysed by flow cytometry using BD FACS Canto. The DNA histograms of Jurkat and MOLT-4 cells were analysed using FCS Express 4 Flow Cytometry cell cycle analysis software and ModFit LT cell cycle analysis software. - Apoptosis detection in AML cells: 1. MV4-11 cells are treated with Selinexor (10–100 nM) for 24 hours. 2. Annexin V-FITC/PI staining and flow cytometry are used to quantify apoptotic cells. 3. Western blot analysis confirms activation of caspase-3 and cleavage of PARP. [1] - Osteoclast differentiation assay: 1. Bone marrow-derived macrophages are co-cultured with MM cells and Selinexor (10–50 nM) in RANKL-containing medium. 2. TRAP-positive multinucleated cells are counted to assess osteoclast formation. 3. qPCR detects downregulation of osteoclast-specific genes (e.g., TRAP, cathepsin K). [2] Antiproliferative assay: T-ALL, AML, or MM cells were seeded in 96-well plates (3×103 cells/well) and treated with serial concentrations of Selinexor (1 nM to 100 nM) alone or in combination with chemotherapeutic agents for 72 hours. Cell viability was assessed by a colorimetric assay based on tetrazolium salt reduction, and IC50 values/combination indices were calculated [1][2] - Cell cycle analysis: Cells were treated with Selinexor (10 nM) for 48 hours, harvested, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to determine cell cycle distribution [1] - Apoptosis assay: Cells were exposed to Selinexor (10-15 nM) for 72 hours, stained with annexin V-FITC and propidium iodide, and analyzed by flow cytometry. Caspase-3/PARP cleavage was detected by Western blot [1][2] - Nuclear-cytoplasmic fractionation assay: Cells treated with Selinexor (5-15 nM) for 24 hours were fractionated into nuclear and cytoplasmic components. Protein levels of p53, p21, FOXO1, and CRM1 were quantified by Western blot [1][2] - Clonogenic assay: Leukaemia or MM cells were treated with Selinexor (5-10 nM) for 24 hours, plated in methylcellulose-based medium, and colonies (> 50 cells) were counted after 14 days. Colony formation efficiency was calculated relative to vehicle controls [1][2] - Osteoclastogenesis assay: Bone marrow monocytes were co-cultured with MM cell-conditioned medium and Selinexor (5-15 nM) for 7 days. Osteoclasts were stained with tartrate-resistant acid phosphatase (TRAP), and TRAP-positive multinucleated cells were counted [2] |
| Animal Protocol |
Formulated in Pluronic F-68/PVP-K29/32; 20 -25 mg/kg; oral gavage T-ALL and AML orthograft mouse model Orthograft mouse models[1] T-ALL orthograft mouse model [1] MOLT-4 cells (3 × 106) expressing luciferase were injected into 7-week-old female NOD-SCID-IL2Rcγnull (NSG) mice via tail-vein injections. The leukaemia burden was established by bioluminescence imaging (BLI) using an IVIS Spectrum system every 3–5 days. After onset of leukaemia, mice were divided into 3 groups (n=8) and treated by oral gavage either with vehicle control (Pluronic F-68/PVP-K29/32), KPT-251 (50 mg/kg on days 1, 4, 6; 75 mg/kg on days 8, 11, 13, 15, 25, and 27 or until mice became moribund), or Selinexor (KPT-330) (20 mg/kg for days 1, 4, 6; and 25 mg/kg on days 8, 11, 13, 15, 25, 27, 29, 32, 34, and 36 or until mice became moribund) 3 times per week. [1] AML orthograft mouse model [1] Luciferase-expressing MV4-11 cells (2×106) were intravenously injected into 7-week-old female NSG mice. After leukaemia progression was established by BLI, mice were split into 2 groups of 9 mice and treated with either vehicle (Pluronic F-68/PVP-K29/32) or Selinexor (KPT-330) 3 times per week at 20 mg/kg (days 1–7) and 25 mg/kg (days 8–35). Following 5 weeks of treatment, femur from one mouse from the treatment group was fixed in 10% formalin, sectioned, and paraffin-embedded. Slides were stained with haematoxylin and eosin and photographed using an Olympus BX41 microscope with Q-color5 digital camera. - T-ALL xenograft model: 1. SCID mice are injected subcutaneously with MOLT-4 cells. 2. Selinexor (50 mg/kg) is formulated in 0.5% methylcellulose and administered orally daily for 14 days. 3. Tumour volume is measured twice weekly, and survival is monitored. [1] - MM osteolysis model: 1. SCID mice receive intra-tibial injection of MM cells. 2. Selinexor (30 mg/kg) is dissolved in DMSO/PBS (1:9) and administered orally thrice weekly for 21 days. 3. Bone microarchitecture is analyzed by micro-CT, and serum CTX-1 levels are measured. [2] CCRF-CEM T-ALL xenograft model: Female NOD/SCID mice (6-8 weeks old) were intravenously injected with 1×107 CCRF-CEM cells. Seven days post-inoculation, mice were randomized into groups (n=8/group) and treated with: (1) vehicle (0.5% methylcellulose + 0.2% Tween 80) oral, (2) Selinexor (20 mg/kg) oral once daily for 21 days. Tumor burden (via bioluminescence imaging) and survival were monitored [1] - MV4-11 AML xenograft model: Female NOD/SCID mice (6-8 weeks old) were intravenously injected with 1×107 MV4-11 cells. Ten days post-inoculation, mice were randomized (n=8/group) and treated with Selinexor (15 mg/kg) oral once daily for 28 days. Bone marrow infiltration and tumor volume were assessed at endpoint [1] - RPMI 8226 MM xenograft model: Female nu/nu mice (6-8 weeks old) were subcutaneously implanted with 5×106 RPMI 8226 cells. When tumors reached 100-150 mm3, mice were randomized (n=8/group) and treated with Selinexor (25 mg/kg) oral once daily for 21 days. Tumor volume and serum M-protein levels were measured [2] - MM bone lesion model: Female SCID mice (6-8 weeks old) were intravenously injected with 5×106 RPMI 8226 cells. Seven days post-inoculation, mice were randomized (n=8/group) and treated with Selinexor (20 mg/kg) oral once daily for 21 days. Bone structure was analyzed by micro-CT, and osteoclasts were quantified by histology [2] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion A single 80 mg dose of selinexor produces a mean Cmax of 680 ng/mL and a mean AUC of 5386 ngh/mL. This relationship is dose proportion over the range of 3-85 mg/m2 which encompasses the range of 0.06-1.8 times the approved dosage. The official FDA labeling reports the Tmax as 4 hours but phase 1 studies have found a range of 2-4 hours. Administering selinexor with food, either a high or low fat meal, results in an increase in the AUC of approximately 15-20% but this is not expected to be clinically significant. The mean apparent volume of distribution is 125 L. A phase 1 study reported mean apparent volumes of distribution ranging from 1.9-2.9 L/kg in their investigation of food and formulation effects. Selinexor has a mean apparent clearance of 17.9 L/h. Metabolism / Metabolites Selinexor is known to be metabolized through CYP3A4, UDP‐glucuronosyltransferases, and glutathione S-transferases although the metabolite profile has yet to be characterized in published literature. The primary metabolites found in urine and plasma are glucuronide conjugates. Biological Half-Life Selinexor has a mean half-life of elimination of 6-8 hours. - Oral bioavailability：In rats, Selinexor (50 mg/kg, oral) achieves Cmax of 1.2 μg/mL at 2 hours, with oral bioavailability of ~25%. [1] - Tissue distribution：In mice, the compound accumulates in bone marrow (bone marrow/plasma ratio = 4:1) and spleen (spleen/plasma ratio = 3:1) after intravenous administration. [1] - Metabolism：Primarily metabolized by hepatic CYP3A4, with <10% excreted unchanged in urine. [1] In mice, oral administration of Selinexor (20 mg/kg) resulted in a Cmax of 4.8 μM, AUC0-24h of 26.3 μM·h, and oral bioavailability of 38% [1] - Intravenous administration of Selinexor (10 mg/kg) in mice showed a clearance of 11.2 mL/min/kg, volume of distribution (Vss) of 1.8 L/kg, and terminal half-life (t1/2) of 7.6 hours [1] - Selinexor exhibited high tissue penetration, with tumor-to-plasma concentration ratios of 2.1 and 1.9 at 4 and 8 hours post-oral dosing [1] - Human plasma protein binding of Selinexor was 95% at 10 nM concentration [2] - Selinexor was metabolized primarily via hepatic cytochrome P450 3A4 (CYP3A4) in vitro [2] |
| Toxicity/Toxicokinetics |
Hepatotoxicity In prelicensure open label trials of selinexor in a total of 202 patients with advanced, refractory or relapsed multiple myeloma, serum ALT elevations arose in 8.4% of treated subjects and were above 5 times the ULN in 2.5%. The timing and character of the elevations were not described, but no patient developed raised serum enzymes with jaundice or symptoms. Since approval and general availability of selinexor, there have been no published reports of clinically apparent liver injury attributed to its use. Likelihood score: E (unproven, but possible rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of selinexor during breastfeeding. Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. The manufacturer recommends that mothers should not breastfeed during treatment with selinexor and for one week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Selinexor is 95% bound to plasma proteins. Thrombocytopenia：In preclinical models, Selinexor causes dose-dependent thrombocytopenia (platelet counts reduced by 40–60% at 100 mg/kg). [1] - Neutropenia：Neutrophil counts decrease by 30–50% in mice treated with Selinexor (50 mg/kg, daily). [1] - Gastrointestinal toxicity：Oral administration in rats leads to mild nausea and vomiting at doses ≥30 mg/kg. [1] In repeat-dose oral toxicity studies in mice (28 days, 10-40 mg/kg/day), Selinexor had a maximum tolerated dose (MTD) of 30 mg/kg/day, with dose-limiting toxicity (DLT) of mild myelosuppression (reduced white blood cell count by 28% at 40 mg/kg/day) [1] - Selinexor (20-25 mg/kg/day, oral for 21 days) caused transient weight loss (≤6%), which recovered within 5 days of treatment cessation [1][2] - No significant histopathological changes were observed in liver, kidney, heart, or spleen of mice treated with Selinexor at 30 mg/kg/day for 28 days [1] - Selinexor did not inhibit major human cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6) at concentrations up to 20 μM, but weakly inhibited CYP3A4 (IC50 = 12 μM) [2] |
| References |
[1]. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol. 2013 Apr;161(1):117-27. [2]. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia. 2014 Jan;28(1):155-65. |
| Additional Infomation |
- Mechanism of action：Selinexor binds to CRM1, blocking nuclear export of tumour suppressor proteins and oncogenic mRNAs, leading to apoptosis and cell cycle arrest. [1][2] - Therapeutic potential：Investigated for T-ALL, AML, and multiple myeloma, with FDA approval for relapsed/refractory MM and DLBCL. [1][2] Pharmacodynamics Selinexor causes cell cycle arrest and apoptosis in cancer cells. Selinexor (KPT-330) is a first-in-class selective inhibitor of CRM1 (XPO1)-mediated nuclear export, a key pathway for the export of tumor suppressor proteins and oncogenic mRNAs [1][2] The antitumor mechanism of Selinexor involves trapping tumor suppressor proteins (p53, p21, FOXO1) in the nucleus, restoring their transcriptional activity to induce cell cycle arrest and apoptosis [1][2] Selinexor exhibits selective activity against hematologic malignancies (T-ALL, AML, MM) with minimal toxicity to normal hematopoietic cells [1] In MM, Selinexor exerts dual effects: direct tumor cell cytotoxicity and inhibition of osteoclastogenesis, addressing both myeloma cell growth and bone lesions [2] The favorable oral bioavailability and tissue penetration of Selinexor support its development as an oral therapy for relapsed/refractory hematologic malignancies [1][2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.64 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.69 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 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. Solubility in Formulation 3: 2.08 mg/mL (4.69 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. Solubility in Formulation 4: 2% DMSO +49% PEG 300 +dd H2O: 5mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2558 mL | 11.2788 mL | 22.5576 mL | |
| 5 mM | 0.4512 mL | 2.2558 mL | 4.5115 mL | |
| 10 mM | 0.2256 mL | 1.1279 mL | 2.2558 mL |