| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
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.
| Targets |
CRM1/chromosome region maintenance 1
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
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. |
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| 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. |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption
Following a single 80 mg dose of celiniso, the mean Cmax was 680 ng/mL and the mean AUC was 5386 ngh/mL. This relationship is dose-proportional within the dose range of 3–85 mg/m², covering 0.06–1.8 times the approved dose. The FDA official label reports a Tmax of 4 hours, but Phase I studies found a range of 2–4 hours. Co-administration of celiniso with food (high-fat or low-fat meals) increases AUC by approximately 15–20%, but this is not expected to be clinically significant. Volume of Distribution The mean apparent volume of distribution is 125 L. A Phase I study reported a mean apparent volume of distribution range of 1.9–2.9 L/kg when investigating the effects of food and formulation. Clearance The mean apparent clearance of celiniso is 17.9 L/h. Metabolism/Metabolites Celenicotinamide is known to be primarily metabolized by CYP3A4, UDP-glucuronyl transferase, and glutathione S-transferase, but its metabolite profile has not been described in detail in published literature. The main metabolite in urine and plasma is glucuronide conjugate. Biological Half-Life The mean elimination half-life of celenicotinamide is 6–8 hours. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
In the pre-marketing open-label trial of selinexor, 202 patients with advanced, refractory, or relapsed multiple myeloma were enrolled. Results showed that 8.4% of subjects experienced elevated serum ALT, with 2.5% of subjects having ALT elevations exceeding 5 times the upper limit of normal (ULN). Although the specific timing and characteristics of the ALT elevation were not described, no patients experienced elevated serum enzymes accompanied by jaundice or other symptoms. No clinically visible cases of liver injury have been reported since selinexor's approval. Probability score: E (Unproven, but likely a rare cause of clinically visible liver injury). Pregnancy and Lactation ◉ Overview of Lactation There is currently no information regarding the use of selinexor during lactation. Most data suggest that breastfeeding is contraindicated during anti-tumor drug treatment in pregnant women. The manufacturer recommends that mothers should not breastfeed during selinexor treatment and for one week after the last dose. Chemotherapy may adversely affect the normal microbiota and chemical composition of breast milk. Women who receive chemotherapy during pregnancy are more likely to experience breastfeeding difficulties. ◉ 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. Protein binding rate Celiniso binds to plasma proteins at a rate of 95%. |
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| References |
[1]. Br J Haematol.2013 Apr;161(1):117-27;[2]. Leukemia.2014 Jan;28(1):155-65. |
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| Additional Infomation |
Selinexor is a triazole compound with the structure 1H-1,2,4-triazole, substituted at positions 1 and 3 with (1Z)-3-oxo-3-[2-(pyrazin-2-yl)hydrazino]prop-1-en-1-yl and 3,5-bis(trifluoromethyl)phenyl, respectively. It is a prescription drug approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma. It has various pharmacological effects, including as an export protein 1 inhibitor, antitumor agent, anti-inflammatory agent, and apoptosis inducer. It belongs to the (trifluoromethyl)benzene, triazole, pyrazine, enamide, and acylhydrazide classes. Selinexor is the first selective nuclear transport inhibitor (SINE) compound. Selinexor, used in combination with bortezomib and dexamethasone, is currently approved for the treatment of multiple myeloma, a cancer formed by antibody-producing plasma cells. This disease is typically treated with high-dose bortezomib and dexamethasone chemotherapy, followed by autologous stem cell transplantation. Other chemotherapy regimens used to treat multiple myeloma include lenalidomide and dexamethasone, thalidomide, and melphalan if the patient is ineligible for transplantation. Selinexor has also received accelerated approval for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two lines of systemic therapy. The U.S. Food and Drug Administration (FDA) approved Selinexor in June 2019. Health Canada approved Selinexor in combination with bortezomib and dexamethasone in June 2022 for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy. Selinexor is a nuclear export inhibitor. Its mechanism of action is as a nuclear export inhibitor. Selinexor is a small molecule nuclear export protein inhibitor, used in combination with dexamethasone for the treatment of relapsed or refractory adult multiple myeloma. The incidence of transient serum enzyme elevations during Selinexor treatment is low, but no clinically significant liver injury with jaundice has been observed. Selinexor is an orally administered small molecule CRM1 (chromosomal region maintenance protein 1, export protein 1, or XPO1) inhibitor with potential antitumor activity. Selinexor irreversibly inhibits the nuclear export of CRM1-mediated cargo proteins (such as tumor suppressor proteins (TSPs), including p53, p21, BRCA1/2, pRB, FOXO, and other growth regulators) by modifying the key cargo-binding residue cysteine 528 of CRM1. Therefore, this drug selectively eliminates tumor cells without damaging normal cells by restoring endogenous tumor suppressor processes through the selective inhibition of nuclear export (SINE). CRM1 is a major export factor of proteins from the nucleus to the cytoplasm and is overexpressed in various cancer cell types.
View MoreDrug Indications The key nuclear export protein CRM1/XPO1 may represent a promising new therapeutic target in human multiple myeloma (MM). We found that chromosomal region maintenance protein 1 (CRM1) is highly expressed in MM patients, plasma cell leukemia cells, and is elevated in cells of patients resistant to bortezomib. CRM1 expression is also associated with exacerbation of osteolytic osteodystrophy and shortened survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel oral irreversible selective nuclear export inhibitors (SINEs) (KPT-185, KPT-330) target CRM1 and induce cytotoxicity in MM cells (ED50 < 200 nM), effective both alone and in co-culture with bone marrow stromal cells (BMSCs) or osteoclasts (OCs). SINEs trigger the accumulation of various CRM1-carrying tumor suppressor proteins in the nucleus, leading to MM cell growth arrest and apoptosis. In addition, SINEs also inhibit the activity of c-myc, Mcl-1, and nuclear factor κB (NF-κB). SINEs induce proteasome-dependent degradation of CRM1 protein; at the same time, they upregulate the transcription of CRM1, p53-targeting genes, apoptosis-related genes, anti-inflammatory genes, and stress-related genes in MM cells. In a mouse model of diffuse human MM bone lesions with SCID, SINEs exhibited potent anti-MM activity, inhibiting MM-induced osteolysis and prolonging survival. In addition, SINEs directly inhibited osteoclastogenesis and bone resorption by blocking RANKL-induced NF-κB and NFATc1, with minimal effect on osteoblasts and bone marrow mesenchymal stem cells (BMSCs). These results support the clinical development of SINE CRM1 antagonists to improve the prognosis of patients with multiple myeloma (MM). [2] |
| Elemental Analysis |
C, 42.56; H, 2.52; Cl, 7.39; F, 23.76; N, 20.44; O, 3.33
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| Related CAS # |
1393477-72-9; 1421923-86-5 (E-isomer); 1621865-82-4 (Z-isomer)
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.62
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| InChi Key |
DEVSOMFAQLZNKR-RJRFIUFISA-N
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| 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-
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| Chemical Name |
(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide hydrochloride
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| Synonyms |
Selinexor HCl; KPT-330 HCl; 1393477-72-9; Xpovio; Selinexor (KPT-330) HCl; KPT 330 HCl; (Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide HCl;
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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