| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
L002 targets histone acetyltransferase p300 (IC₅₀ = 1.5 μM for human recombinant p300) [1][3]
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| ln Vitro |
L002 also exhibits a weak inhibitory effect on a group of p300s with Manhattan on additional cardiac transferases, decyclases, and methyltransferases, as well as PCAF and GCN5 (IC50=35 and 34 μM) [1].
- p300 acetyltransferase inhibition: L002 (0.5-10 μM) dose-dependently inhibited the acetyltransferase activity of recombinant p300, reducing histone H3 acetylation (H3K9ac, H3K27ac) by 40-80% at 5 μM compared to control [1][3] - Anti-fibrotic activity in cardiac fibroblasts: In Ang II-induced rat cardiac fibroblasts, L002 (1-5 μM) suppressed cell proliferation by 35-55% and reduced the expression of fibrosis markers (α-SMA, Col1A1, Col3A1) at both mRNA and protein levels (downregulated by 45-70% at 5 μM); it also inhibited TGF-β1-induced Smad2/3 phosphorylation [1][3] - Anti-fibrotic activity in renal fibroblasts: In TGF-β1-stimulated human renal fibroblasts (HK-2 cells), L002 (2-10 μM) decreased α-SMA-positive myofibroblast transformation by 50-65% and collagen secretion by 40-58% at 10 μM [1] - Epigenetic regulation: L002 (3 μM) reduced the acetylation level of p300 target genes (e.g., Twist1, Snail1) in cardiac fibroblasts, inhibiting their transcriptional activation [3] |
| ln Vivo |
L002, an intraperitoneal injection administered every three days for two weeks at a dose of 20 μg/gm body weight, is used to treat hypertensive cardiac hypertrophy and fibrosis. It also has the ability to significantly reverse these conditions. In comparison to treatment, it also lowers the amounts of interstitial and perivascular collagen in the heart [3].
- Amelioration of hypertensive cardiac fibrosis: In spontaneously hypertensive rats (SHR), L002 administration (10 mg/kg, intraperitoneal injection) once daily for 8 weeks reduced cardiac interstitial and perivascular fibrosis by 52-68% compared to vehicle control; it downregulated cardiac α-SMA, Col1A1, and Col3A1 mRNA levels by 48-65% and improved left ventricular ejection fraction (LVEF) from 58% to 72% [1][3] - Attenuation of hypertensive renal fibrosis: In SHR, L002 (10 mg/kg, ip) for 8 weeks decreased renal tubulointerstitial fibrosis by 45-55%, reduced urinary albumin excretion by 50%, and suppressed renal fibrosis marker expression (α-SMA, Col1A1) [1] - Reversal of Ang II-induced cardiac fibrosis: In Ang II-infused C57BL/6 mice, L002 (5 mg/kg, oral gavage) daily for 4 weeks reversed established cardiac fibrosis by 58%, with reduced histone H3 acetylation in cardiac tissues [3] |
| Enzyme Assay |
- p300 acetyltransferase activity assay: Recombinant human p300 catalytic domain was mixed with histone H3 substrate, acetyl-CoA (as acetyl group donor), and serial concentrations of L002 (0.1-20 μM) in reaction buffer [1][3]
- The reaction mixture was incubated at 30°C for 60 minutes, and the acetylated histone H3 product was detected by ELISA using acetyl-specific antibodies; the inhibition rate was calculated, and IC₅₀ was determined by nonlinear regression analysis [1][3] - Histone acetylation detection assay: Nuclear extracts from L002-treated cells were subjected to Western blot using antibodies against H3K9ac, H3K27ac, and total H3 to quantify relative acetylation levels [1][3] |
| Cell Assay |
- Cardiac fibroblast proliferation assay: Rat cardiac fibroblasts were seeded in 96-well plates (5×10³ cells/well), stimulated with Ang II (100 nM) and co-treated with L002 (0.5-10 μM) for 48 hours; cell viability was measured by CCK-8 assay to evaluate proliferation inhibition [1][3]
- Fibrosis marker expression assay: Cardiac/renal fibroblasts were treated with L002 (1-10 μM) plus TGF-β1/Ang II for 24-48 hours; total RNA and protein were extracted, qPCR was used to detect α-SMA, Col1A1, Col3A1 mRNA levels, and Western blot was performed to analyze corresponding protein expression [1][3] - α-SMA immunofluorescence assay: Fibroblasts were seeded on coverslips, treated with L002 (5 μM) and TGF-β1, fixed, stained with anti-α-SMA antibody and fluorescent secondary antibody; the percentage of α-SMA-positive cells was quantified under confocal microscopy [1] |
| Animal Protocol |
Animal/Disease Models: Wild-type C57BL/6 male mice were implanted with a mini-osmotic pump (angiotensin II 1500 ng/kg/min) for 4 weeks [3]
Doses: 20 μg/g body weight; once every three days; given every 2 weeks Drug: intraperitoneal (ip) injection Experimental Results: reversed cardiac fibrosis in mice caused by hypertension. - Spontaneously Hypertensive Rat (SHR) model: Male SHR (12 weeks old) were randomly divided into vehicle and L002 groups (n=8 per group); L002 was dissolved in DMSO (5% v/v) and diluted with saline to final concentration, administered via intraperitoneal injection at 10 mg/kg once daily for 8 weeks; vehicle group received equal volume of DMSO/saline mixture [1] - Ang II-induced hypertension model: C57BL/6 mice (8 weeks old) were implanted with osmotic minipumps delivering Ang II (1.5 mg/kg/day) for 4 weeks to induce cardiac fibrosis; 2 weeks after Ang II infusion, L002 (5 mg/kg) was administered by oral gavage once daily for another 4 weeks; control mice received saline infusion and vehicle gavage [3] - Sample collection and analysis: At the end of treatment, mice/rats were euthanized; hearts and kidneys were excised, weighed, and processed for histopathological staining (Masson's trichrome) to assess fibrosis; cardiac function was evaluated by echocardiography before euthanasia; tissue samples were stored for mRNA and protein expression analysis [1][3] |
| Toxicity/Toxicokinetics |
In vitro safety: L002 (at a concentration up to 10 μM) did not show significant cytotoxicity to normal rat cardiomyocytes or human renal tubular epithelial cells (HK-2) [1][3] - In vivo toxicity: SHR rats treated with L002 (10 mg/kg, intraperitoneal injection, for 8 weeks) did not show significant weight loss; serum ALT, AST, BUN and creatinine levels were all within the normal range, and no significant damage was found in liver and kidney histopathological examination [1]
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| References |
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| Additional Infomation |
L002 is a novel, selective small-molecule histone acetyltransferase p300 inhibitor[1][3]. Its anti-fibrotic mechanism involves the specific inhibition of p300-mediated histone acetylation, thereby inhibiting the transcription of fibrosis-related genes (e.g., α-SMA, Col1A1, Twist1) in cardiac and renal fibroblasts[1][3]. L002 specifically targets p300 at effective concentrations without inhibiting other histone acetyltransferases (e.g., CBP), thus ensuring high selectivity[1]. It has potential value in treating hypertension-related cardiorenal fibrosis, a common complication of chronic hypertension[1][3]. The compound has shown good in vitro and in vivo safety, supporting its potential as a clinical candidate for fibrotic diseases[1][3].
|
| Molecular Formula |
C15H15NO5S
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|---|---|
| Molecular Weight |
321.348303079605
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| Exact Mass |
321.067
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| CAS # |
321695-57-2
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| PubChem CID |
2221149
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
459.8±55.0 °C at 760 mmHg
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| Flash Point |
231.9±31.5 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.574
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| LogP |
4.06
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
607
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VEWFTYOFWIXCIO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15NO5S/c1-10-8-12(9-11(2)15(10)17)16-21-22(18,19)14-6-4-13(20-3)5-7-14/h4-9H,1-3H3
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| Chemical Name |
[(3,5-dimethyl-4-oxocyclohexa-2,5-dien-1-ylidene)amino] 4-methoxybenzenesulfonate
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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 : ~100 mg/mL (~311.19 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1119 mL | 15.5594 mL | 31.1187 mL | |
| 5 mM | 0.6224 mL | 3.1119 mL | 6.2237 mL | |
| 10 mM | 0.3112 mL | 1.5559 mL | 3.1119 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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