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| Targets |
The primary target of KL-1 is the super elongation complex (SEC), a critical regulator of transcriptional elongation and gene expression. SEC is a multi-subunit complex that includes the scaffolding protein AFF4 and the kinase P-TEFb. KL-1 is a potent and specific SEC inhibitor that disrupts the interaction between AFF4 and P-TEFb. By disrupting this interaction, KL-1 impairs the release of Pol II from promoter-proximal pause sites and reduces the average rate of processive transcription elongation. This leads to suppression of transcription of oncogenes and other genes essential for tumor cell survival.
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| ln Vitro |
KL-1 is a potent and specific SEC inhibitor that disrupts the interaction between the SEC scaffolding protein AFF4 and P-TEFb. This disruption causes Pol II to detach from the promoter-proximal region and impairs the release of Pol II from promoter-proximal pause sites. The compound promotes apoptosis and has anti-tumor activity. By inhibiting SEC, KL-1 can suppress the transcription of oncogenes and other genes essential for tumor cell survival. Its specificity for SEC makes it a valuable tool for studying transcriptional regulation and cancer biology.
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| ln Vivo |
No specific in vivo activity data is publicly available for KL-1. As an SEC inhibitor, it would be expected to have anti-tumor activity in vivo. The compound's ability to promote apoptosis suggests potential efficacy in cancer models. By suppressing transcription of oncogenes, KL-1 could inhibit tumor growth and progression. However, specific in vivo studies have not been detailed in the available literature.
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| Enzyme Assay |
No specific non-cell assay protocol is available for KL-1. For SEC inhibitors, standard cell-free assays include measuring the interaction between AFF4 and P-TEFb using techniques such as fluorescence polarization, AlphaScreen, or ELISA. The compound is incubated with the proteins, and the inhibition of interaction is measured to determine potency. Surface plasmon resonance (SPR) can be used to measure binding affinity and kinetics. These assays provide mechanistic insights into how the compound disrupts the SEC.
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| Cell Assay |
No specific cell-based assay protocol is available for KL-1. For SEC inhibitors, standard cellular assays involve treatment of cells with the compound and measurement of transcriptional elongation. Pol II promoter-proximal pausing and release can be assessed by ChIP-seq or ChIP-qPCR using antibodies against Pol II. Transcription of SEC-dependent genes (e.g., MYC, other oncogenes) can be measured by qPCR. Apoptosis is assessed by Annexin V/PI staining or caspase activity assays. Cell viability is measured using MTT or CellTiter-Glo assays.
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| Animal Protocol |
No specific animal protocol is available for KL-1. For anti-tumor studies, standard in vivo models include xenograft models using cancer cell lines sensitive to SEC inhibition. KL-1 is administered (route and dose to be determined) for 2-4 weeks. Tumor growth, apoptosis markers, and survival are assessed. The compound's effects on transcription of oncogenes and other SEC-dependent genes can be evaluated in tumor tissues. However, specific protocols have not been detailed in the available literature.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KL-1. The compound has a molecular weight of 345.78 and formula C18H16ClNO4. It is soluble in DMSO at 39 mg/mL and should be stored at -20°C for long-term stability. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KL-1. As a research compound, standard preclinical toxicology would be required for therapeutic development. The compound's mechanism of action as a transcriptional inhibitor suggests potential for effects on normal cells that depend on SEC-dependent transcription. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
KL-1 is also known as SEC inhibitor KL-1. It has the molecular formula C18H16ClNO4 and molecular weight 345.78. It is a peptidomimetic lead compound and a potent and specific SEC inhibitor that disrupts the interaction between AFF4 and P-TEFb. The compound promotes apoptosis and has anti-tumor activity. It is soluble in DMSO at 39 mg/mL. Powder can be stored at -20°C for 3 years or at 4°C for 2 years; in solvent at -80°C for 6 months or at -20°C for 1 month. No clinical trial status has been identified.
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| Molecular Formula |
C18H16CLNO4
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|---|---|
| Molecular Weight |
345.776944160461
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| Exact Mass |
345.076
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| CAS # |
900308-84-1
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| PubChem CID |
46248683
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)Cl)NC(=O)C(=O)/C=C(/C2=CC(=CC=C2)OC)\O
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| InChi Key |
ARTVILCEXNCVIN-YBEGLDIGSA-N
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| InChi Code |
InChI=1S/C18H16ClNO4/c1-11-6-7-13(19)9-15(11)20-18(23)17(22)10-16(21)12-4-3-5-14(8-12)24-2/h3-10,21H,1-2H3,(H,20,23)/b16-10-
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| Chemical Name |
(Z)-N-(5-chloro-2-methylphenyl)-4-hydroxy-4-(3-methoxyphenyl)-2-oxobut-3-enamide
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| Synonyms |
KL-1; KL 1; KL1
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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) |
DMSO : ~41.67 mg/mL (~120.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.02 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. Solubility in Formulation 2: ≥ 2.08 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8920 mL | 14.4601 mL | 28.9201 mL | |
| 5 mM | 0.5784 mL | 2.8920 mL | 5.7840 mL | |
| 10 mM | 0.2892 mL | 1.4460 mL | 2.8920 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.
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