| Size | Price | Stock | Qty |
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| Other Sizes |
Purity: ≥98%
| Targets |
PI3Kδ (IC50 = 25 nM); PI3Kγ (IC50 = 33 nM)
Tenalisib targets PI3Kδ and PI3Kγ, two isoforms of the PI3K family that are important for immune cell signaling and survival. It inhibits PI3Kδ with an IC50 of 24.5 nM and PI3Kγ with an IC50 of 33.2 nM. The compound shows selectivity over PI3Kα (>300-fold) and PI3Kβ (>100-fold). |
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| ln Vitro |
Tenalisib shows selectivity over PI3K α (>300-fold) and β (>100-fold) isoforms. In both HEL-RS and HEL-RR cells, tenalisib mildly inhibits proliferation (33-46% inhibition @ 10 μM). Inhibition of proliferation is nearly 100% (>90% for HEL-RS and >70% for HEL-RR) when 10 μM tenalisib is added to ruxolitinib. The EC50 of ruxolitinib (5.8 μM ) in HEL-RR cells is significantly decreased by the addition of 5 μM tenalisib 4 hours before the addition of ruxolitinib. When 10 μM tenalisib and ruxolitinib are combined for 72 hours, more cells undergo apoptosis (55% in HEL-RS and 37% in HEL-RR) than when either agent is used alone (16-27% in HEL-RS and 17-21% in HEL-RR)[1].
Tenalisib inhibits PI3Kδ and PI3Kγ with IC50 values of 24.5 nM and 33.2 nM, respectively. It exhibits modest proliferation inhibition (33-46% inhibition at 10 μM) in both HEL-RS and HEL-RR cells. The combination of 10 μM tenalisib and ruxolitinib inhibits proliferation almost completely (>90% for HEL-RS and >70% for HEL-RR). |
| ln Vivo |
Tenalisib has been well tolerated in subjects with heavily pre-treated relapsed/refractory hematologic malignancies. With no DLTs, reported toxicities are controllable. At less than 200 mg BID, single agent activity can be seen in patients who are challenging to treat[2].
In vivo, Tenalisib has been well tolerated in subjects with heavily pre-treated relapsed/refractory hematologic malignancies. With no dose-limiting toxicities reported, toxicities are controllable. At less than 200 mg BID, single agent activity can be seen in patients who are challenging to treat. |
| Enzyme Assay |
Myelofibrosis (MF) represents a life-threatening neoplasm that manifests particularly in the elderly population and is characterized by bone marrow fibrosis and extramedullary hematopoeisis. While ruxolitinib, a JAK1/2 inhibitor, has recently been approved by the USFDA for its disease modifying potential in MF patients, it is still not considered as a curative option. Targeting another kinase such as PI3K, downstream of JAK, could therefore be a more efficient way of treating myelofibrotic neoplasms. RP6530 is a novel, potent, and selective PI3K δ/γ inhibitor that demonstrated high potency against PI3Kδ (IC50 = 25 nM) and γ (IC50 = 33 nM) enzymes with selectivity over α (>300-fold) and β (>100-fold) isoforms. The objective of this study was to evaluate the effect of a combination of ruxolitinib and RP6530 in the JAK2-V617F mutant Human Erythroleukemia (HEL) cell line[1].
Cell-free kinase assays for Tenalisib utilize purified recombinant PI3Kδ and PI3Kγ enzymes and phosphatidylinositol substrates. The kinase reaction is performed in the presence of ATP and increasing concentrations of the compound. Phosphorylation of the substrate is quantified using radiometric or fluorescence-based detection. IC50 values are determined from concentration-response curves. |
| Cell Assay |
Potential of the combination (1 μM RP6530 + BORT between 0.1 nM and 1 μM) is studied in MM cell lines, namely, MM-1S and MM-1R. After incubating with the compound for 72 hours at 37°C, proliferation is assessed using a MTT assay. The combination's apoptotic potential is calculated using AnnexinV/PI staining.
HEL-RS and HEL-RR cells (myelofibrosis models) or other hematologic cancer cell lines are treated with Tenalisib at various concentrations (typically 1-10 μM). Cell proliferation is assessed by MTT or CellTiter-Glo assays. Apoptosis is measured by Annexin V staining or caspase activation. Combination studies with ruxolitinib are performed to assess synergistic effects. |
| Animal Protocol |
3 mg/kg | Rats, dogs
The dose escalation will determine the maximum tolerated dose (MTD) of RP6530 using a standard 3+3 design. Patients (pts) with a confirmed diagnosis of hematological malignancy and at least one prior therapy are eligible. Additional eligibility criteria include an ECOG performance status ≤ 2, measurable/evaluable disease, and life expectancy of at least 12 weeks. Primary endpoints are safety and pharmacokinetic (PK) and are supported by secondary endpoints such as pharmacodynamic and efficacy parameters (overall and complete response rates) and correlative biomarkers. RP6530 is given orally twice daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal from study. The study is designed to enroll up to 120 pts in the dose-escalation and expansion phase. Adverse events (AE) are assessed using the CTCAE v4.0/IWCLL guidelines as applicable. Efficacy evaluations are conducted every 8 wks.[2]
| ADME/Pharmacokinetics |
Tenalisib is orally bioavailable. As a small molecule (MW 443.43, formula C23H18FN5O3), it has favorable drug-like properties. The compound is soluble in DMSO. PK parameters including Tmax, half-life, clearance, and bioavailability have been characterized in preclinical species and in humans.
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| Toxicity/Toxicokinetics |
Tenalisib has been well tolerated in clinical studies with manageable toxicities. As a PI3Kδ/γ inhibitor, it has potential for immunosuppression and other class-related adverse events. Standard toxicological assessments including genotoxicity, reproductive toxicity, and chronic toxicity studies have been conducted to support clinical development.
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| References |
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| Additional Infomation |
Tenalisib is currently undergoing clinical trial NCT03711604 (Tenalisib (RP6530) Compassionate Use Study). Tenalisib is an orally potent, highly selective small-molecule inhibitor of phosphatidylinositol-3 kinase (PI3K) δ and γ isoforms with potential immunomodulatory and antitumor activities. After administration, tenalisib inhibits PI3K δ and γ isoforms and blocks the activation of the PI3K/AKT-mediated signaling pathway. This may lead to reduced proliferation of tumor cells expressing PI3K δ/γ. Furthermore, the drug modulates inflammatory responses through multiple mechanisms, including inhibiting the release of reactive oxygen species (ROS) from neutrophils and inhibiting the activity of tumor necrosis factor (TNF)-α. Unlike other PI3K isoforms, δ and γ isoforms are primarily overexpressed in hematologic malignancies as well as inflammatory and autoimmune diseases. By selectively targeting these isoforms, the PI3K signaling pathway in normal non-tumor cells is minimally or completely unaffected, thus minimizing the drug's side effects.
Tenalisib (molecular formula C23H18FN5O3, MW 443.43) is also known as RP6530. It is a potent and selective dual PI3Kδ/γ inhibitor with IC50 values of 24.5 nM and 33.2 nM, respectively. The compound shows >300-fold selectivity for PI3Kδ and >100-fold selectivity for PI3Kγ over other isoforms. It is intended for research use only. |
| Molecular Formula |
C23H18FN5O2
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| Molecular Weight |
415.42
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| Exact Mass |
415.144
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| Elemental Analysis |
C, 66.50; H, 4.37; F, 4.57; N, 16.86; O, 7.70
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| CAS # |
1639417-53-0
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| Related CAS # |
Tenalisib R Enantiomer;1639417-54-1; 1639417-53-0; 1693773-94-2
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| PubChem CID |
86291103
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| Appearance |
white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.715
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| LogP |
5.11
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
704
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=C([H])C([H])=C([H])C(=C1[H])C1C(C2=C([H])C([H])=C([H])C([H])=C2OC=1[C@]([H])(C([H])([H])C([H])([H])[H])N([H])C1C2=C(N=C([H])N=1)N=C([H])N2[H])=O
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| InChi Key |
HDXDQPRPFRKGKZ-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C23H18FN5O2/c1-2-16(29-23-19-22(26-11-25-19)27-12-28-23)21-18(13-6-5-7-14(24)10-13)20(30)15-8-3-4-9-17(15)31-21/h3-12,16H,2H2,1H3,(H2,25,26,27,28,29)/t16-/m0/s1
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 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 25.0 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 2: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4072 mL | 12.0360 mL | 24.0720 mL | |
| 5 mM | 0.4814 mL | 2.4072 mL | 4.8144 mL | |
| 10 mM | 0.2407 mL | 1.2036 mL | 2.4072 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04204057 | Completed | Drug: Tenalisib | Leukemia, Lymphocytic, Chronic, B-Cell | Rhizen Pharmaceuticals SA | November 28, 2019 | Phase 2 |
| NCT03711578 | Completed | Drug: Tenalisib | Non Hodgkin Lymphoma | Rhizen Pharmaceuticals SA | November 25, 2018 | Phase 2 |
| NCT03770000 | Completed | Drug: Tenalisib Drug: Romidepsin |
T Cell Lymphoma | Rhizen Pharmaceuticals SA | March 12, 2019 | Phase 1 Phase 2 |
| NCT03711604 | Completed | Drug: Tenalisib | Hematological Malignancies | Rhizen Pharmaceuticals SA | November 28, 2018 | Phase 1 Phase 2 |
| NCT05239910 | Withdrawn | Drug: Tenalisib | Peripheral T Cell Lymphoma | Rhizen Pharmaceuticals SA | January 2023 | Phase 2 |
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