1. What Is Oroxylin A?
Oroxylin A (5,7-dihydroxy-6-methoxyflavone), also known as Baicalein 6-methyl ether or 6-Methoxybaicalein, is an O-methylated flavone naturally abundant in the root of Scutellaria baicalensis Georgi (Chinese skullcap / Huang-Qin) and the bark of Oroxylum indicum (Indian trumpet flower). Unlike most plant-derived flavonoids whose pharmacological scope is confined to a single pathway, Oroxylin A operates across two mechanistically independent research domains: oncology (via CDK9 and transketolase inhibition) and neuroscience (via dopamine reuptake inhibition and GABA-A negative allosteric modulation). This dual identity — a metabolic vulnerability disruptor in cancer cells and a neurotransmitter modulator in the CNS — has made Oroxylin A one of the most intensively studied natural flavones of the past decade, with over 200 PubMed-indexed publications since 2010 and an active Phase I clinical trial for hepatocellular carcinoma (NMPA: ChiCTR2100051434).
2. Physicochemical Data & Product Specifications
2.1 Identity & Structure
| Common Name | Oroxylin A |
| Synonyms | Baicalein 6-methyl ether; 6-Methoxybaicalein; 5,7-Dihydroxy-6-methoxyflavone; Oroxylin; 5,7-Dihydroxy-6-methoxy-2-phenyl-4H-1-benzopyran-4-one |
| CAS Number | 480-11-5 |
| Molecular Formula | C₁₆H₁₂O₅ |
| Molecular Weight | 284.26 g/mol |
| Chemical Class | O-methylated flavone (flavonoid) |
| Natural Source | Scutellaria baicalensis, Scutellaria lateriflora, Oroxylum indicum |
| IUPAC Name | 5,7-Dihydroxy-6-methoxy-2-phenyl-4H-chromen-4-one |
| SMILES | COC1=C(C=C2C(=C1O)C(=O)C=C(O2)C3=CC=CC=C3)O |
| InChIKey | LKOJGSWUMISDOF-UHFFFAOYSA-N |
| PubChem CID | 5320315 |
| ChEMBL ID | CHEMBL183513 |
2.2 Physicochemical Properties
| Appearance | Yellow to pale yellow crystalline powder |
| Purity (HPLC) | ≥99% (area normalization, 254 nm) |
| Melting Point | 195–197 °C (literature); range can extend to 232 °C depending on polymorph |
| Density | 1.4 ± 0.1 g/cm³ (predicted) |
| Boiling Point | 540.9 ± 50.0 °C (predicted, 760 mmHg) |
| Flash Point | 207.4 ± 23.6 °C |
| LogP | 2.88 (moderate lipophilicity) |
| PSA (Polar Surface Area) | 79.90 Ų |
2.3 Solubility Profile
| DMSO | ≥30 mg/mL (105.5 mM) — recommended for stock solutions |
| Ethanol | Sparingly soluble; gentle warming recommended |
| Water | Practically insoluble; aqueous formulations require co-solvent (e.g., <0.5% DMSO or cyclodextrin encapsulation) |
| DMF | Soluble; suitable for certain organic-phase assays |
3. Mechanism of Action: Two Axes, One Molecule
Oroxylin A's unusual breadth of pharmacological activity stems from its ability to engage targets in two distinct biological compartments — the intracellular kinase/metabolic network and the synaptic neurotransmitter milieu — simultaneously. These two axes are mechanistically independent and supported by separate bodies of peer-reviewed evidence.
3.1 Axis I — Anticancer Mechanisms
3.1.1 CDK9 Inhibition → p53 Stabilization
In hepatocellular carcinoma (HCC) cells harboring wild-type TP53, Oroxylin A acts as a novel CDK9 inhibitor (Wei et al., 2022, Acta Pharmacologica Sinica). Inhibition of CDK9 disrupts the phosphorylation-dependent regulation of MDM2 and SIRT1, two principal negative regulators of p53. The net effect is dual suppression of p53 degradation (via MDM2 downregulation) and p53 deacetylation (via SIRT1 inhibition), resulting in sustained p53 protein stabilization and transcriptional activation of downstream targets including p21, PUMA, and TIGAR. This mechanism has been validated in HepG2, Huh7, and patient-derived organoid models.
3.1.2 Transketolase (TKT) Inhibition → Non-Oxidative PPP Suppression
A landmark 2022 study in Clinical and Translational Medicine identified Oroxylin A as a first-in-class TKT inhibitor (a thiamine pyrophosphate-dependent enzyme of the non-oxidative pentose phosphate pathway). By binding TKT, Oroxylin A suppresses ribose-5-phosphate (R5P) production for nucleotide synthesis in rapidly dividing cancer cells, creating a metabolic vulnerability distinct from conventional glycolytic inhibitors. Transcriptomic profiling confirmed downstream activation of p53 signaling, likely triggered by R5P accumulation and genomic stress. This mechanism was validated in both mouse xenograft models and HCC patient-derived organoids (PDOs), demonstrating translational relevance beyond immortalized cell lines.
3.1.3 SIRT3-Mediated Metabolic Reprogramming
In breast cancer models (MCF-7), Oroxylin A upregulates SIRT3, a mitochondrial NAD⫀-dependent deacetylase. SIRT3 deacetylates and activates FOXO3a, which translocates to the nucleus and drives SOD2 transcription. Elevated SOD2 scavenges mitochondrial ROS, indirectly promoting HIF-1α destabilization and suppressing glycolysis-dependent proliferation (Wei et al., 2015, Cell Death & Disease). This SIRT3-FOXO3a-SOD2-HIF-1α axis represents a non-canonical metabolic checkpoint distinct from the CDK9/p53 pathway.
3.1.4 p53 Mitochondrial Translocation & Apoptosis
In colon cancer cells (HCT-116), Oroxylin A induces p53 translocation to mitochondria, where it forms a complex with Recql4 and inhibits SOD2 activity, triggering mitochondrial ROS overload, membrane potential collapse, and intrinsic apoptosis (Qiao et al., 2016, Oncotarget). This mitochondrial p53 mechanism is validated in vivo and is independent of the transcriptional p53 pathway described above.
Inhibition
SIRT1 ↓
Stabilized
& Cell Cycle Arrest
Inhibition
PPP Blocked
Synthesis ↓
Suppressed
3.2 Axis II — Neuroprotection & Cognitive Mechanisms
3.2.1 Dopamine Reuptake Inhibition (DRI)
Yoon et al. (2013, Archives of Pharmacal Research) demonstrated that Oroxylin A inhibits dopamine reuptake in vitro, producing a functional increase in synaptic dopamine availability. In the spontaneously hypertensive rat (SHR) model of attention deficit hyperactivity disorder (ADHD), Oroxylin A improved behavioral measures of attention and impulsivity. Unlike amphetamine-class DRIs, Oroxylin A's noradrenergic effects are modest, yielding a "low-arousal" stimulant profile described as clear-headed wakefulness without peripheral jitteriness.
3.2.2 GABA-A Negative Allosteric Modulation (NAM)
Liao et al. (1998, Planta Medica) identified Oroxylin A as a negative allosteric modulator at the benzodiazepine site of the GABA-A receptor. This property reduces tonic GABAergic inhibition, indirectly disinhibiting glutamatergic and dopaminergic circuits. The GABA-A NAM activity is believed to underlie the compound's pro-cognitive and alertness-enhancing effects, and is distinct from classical anxiogenic NAMs (e.g., DMCM) in that Oroxylin A does not appear to produce anxiety at behaviorally relevant doses.
3.2.3 BDNF Upregulation via MAPK-CREB
Jeon et al. (2011, Neuroscience Research) established that Oroxylin A induces sustained BDNF expression in rat primary cortical neurons through a GABA-A blockade → synaptic NMDA receptor activation → Ca²+ influx → ERK1/2 MAPK phosphorylation → CREB Ser133 phosphorylation cascade. This pathway was blocked by the NMDA antagonist MK-801, TTX, and the MEK inhibitor PD98059, confirming the sequential dependency.
3.2.4 Adenosine A2A Receptor-Mediated BDNF Induction
An independent study (Jeon et al., 2014) showed Oroxylin A also stimulates BDNF expression on cortical neurons via adenosine A2A receptor activation, providing a second, GABA-independent route to neurotrophin upregulation. This A2A-BDNF axis is particularly relevant for memory consolidation — Kim et al. (2014, Brain Research Bulletin) demonstrated that Oroxylin A enhanced memory consolidation in mice in a BDNF-dependent manner.
3.3 BDNF & Neurotrophic Factor Upregulation Data
| Factor | Fold Change | Model System | Key Reference |
|---|---|---|---|
| BDNF (protein) | ~2× ↑ | Rat primary cortical neurons (3–48 h) | Jeon et al., 2011 |
| p-CREB (Ser133) | Concentration- & time-dependent ↑ | Rat primary cortical neurons | Jeon et al., 2011 |
| p-ERK1/2 | Sustained activation | Rat primary cortical neurons | Jeon et al., 2011 |
| Memory consolidation | Significant improvement | ICR mice (passive avoidance) | Kim et al., 2014 |
| Aβ(25-35) memory impairment | Ameliorated (acute & repeated) | ICR mice | Kim et al., 2014 |
| ADHD-like behavior (SHR) | Significant improvement | SHR rat model | Yoon et al., 2013 |
4. Core Advantages — Why Oroxylin A?
Dual-Domain Mechanism
Validated in both oncology (CDK9/TKT/p53) and neuroscience (DRI/GABA-A/BDNF) with independent peer-reviewed evidence — rare for a single natural compound.
Clinical-Stage Candidate
Active Phase I trial (ChiCTR2100051434) for HCC. PDO and xenograft validation provides translational confidence for preclinical research programs.
Metabolic + Genetic Dual Hit
TKT inhibition (metabolic) + CDK9 inhibition (genetic p53 restoration) provides two orthogonal vulnerabilities that cancer cells cannot easily bypass via single-pathway compensation.
Non-Psychostimulant Cognitive Profile
Dopamine reuptake inhibition with minimal noradrenergic activation; GABA-A NAM for disinhibition; BDNF upregulation for plasticity — three mechanisms, no amphetamine-like peripheral side effects.
Natural Origin, Defined Purity
Extracted from S. baicalensis with centuries of traditional use history. ≥99% HPLC purity ensures batch-to-batch reproducibility for quantitative pharmacology.
Rich Literature Foundation
200+ PubMed publications since 2010; mechanism targets validated by siRNA knockdown, pharmacological inhibitors, and genetic models.
4.1 Oroxylin A vs. Related Flavonoids: Mechanistic Comparison
| Parameter | Oroxylin A | Baicalein | Wogonin | Baicalin |
|---|---|---|---|---|
| CAS | 480-11-5 | 491-67-8 | 632-85-9 | 21967-41-9 |
| 6-OCH₃ Substitution | ✓ (Defining feature) | ✗ | 8-OCH₃ | ✗ (7-O-Glucuronide) |
| CDK9 Inhibition | ✓ Validated (Wei 2022) | ~Partial | ✗ | ✗ |
| TKT Inhibition | ✓ First-in-class (2022) | ✗ | ✗ | ✗ |
| Dopamine Reuptake Inhibition | ✓ (Yoon 2013) | ✗ | ✗ | ✗ |
| GABA-A NAM | ✓ (Liao 1998) | ~Partial | ✓ | ✗ |
| BDNF Upregulation | ✓ MAPK-CREB (Jeon 2011) | ✗ | ✗ | ✗ |
| p53 Stabilization | ✓ MDM2 + SIRT1 dual (2022) | ~Partial | ✗ | ✗ |
| SIRT3 Activation | ✓ (Wei 2015) | ✗ | ✗ | ✗ |
| Clinical Trial Status | Phase I HCC (NMPA) | None | None | None |
| BBB Penetration | ✓ (moderate LogP) | ✓ | ✓ | ✗ (ionized glucuronide) |
| Oral Bioavailability | Moderate (glucuronidation) | Moderate | Low–Moderate | Low (prodrug) |
5. Research Applications
Hepatocellular Carcinoma (HCC) Research
CDK9 inhibition → p53 restoration in wt-p53 HCC models; TKT inhibition → nucleotide synthesis blockade. Validated in HepG2, Huh7, and patient-derived organoids. Phase I clinical candidate.
Breast Cancer Metabolism
SIRT3-FOXO3a-SOD2-HIF-1α axis; glycolysis-dependent proliferation suppression in MCF-7. In vivo xenograft validation with 43.95% tumor growth inhibition at 100 mg/kg IV.
Colorectal Cancer Apoptosis
p53 mitochondrial translocation + Recql4 complex formation → SOD2 inhibition → ROS overload → intrinsic apoptosis. Validated in HCT-116 in vitro and in vivo.
Neuroprotection & Cognitive Enhancement
BDNF upregulation via MAPK-CREB and A2A pathways; Aβ(25-35) memory impairment amelioration; dopamine reuptake inhibition for attention. Mouse passive avoidance and SHR ADHD models.
Kinase Inhibitor Screening & CDK Biology
Use Oroxylin A as a reference CDK9 inhibitor in kinase profiling panels, p53 signaling pathway dissection, and CDK9-dependent transcriptional regulation studies.
Metabolic Enzyme Targeting
First-in-class TKT inhibitor for pentose phosphate pathway research; metabolic flux analysis; nucleotide synthesis vulnerability studies; Warburg effect counter-screening.
5.1 Recommended Working Concentrations
| In vitro — CDK9/p53 pathway | 50–200 μM (cell-type dependent; 100 μM typical for HCT-116, HepG2) |
| In vitro — BDNF induction | 10–50 μM (rat primary cortical neurons, 3–48 h exposure) |
| In vitro — TKT inhibition | IC₅₀ determined by cell line; enzyme assay conditions per literature |
| In vivo — Xenograft (IV) | 100 mg/kg (MCF-7, HCT-116 mouse models) |
| Stock solution | 30–50 mg/mL in DMSO; store aliquots at −80 °C; avoid freeze-thaw cycles |
6. Packaging, Storage & Logistics Compliance
6.1 Storage Conditions
| Recommended Temperature | 2–8 °C (refrigerated), sealed container, protected from light |
| Long-Term Storage | −20 °C for >6 months; desiccated, argon-purged vial recommended |
| Shelf Life (Powder) | ≥24 months at 2–8 °C under recommended conditions |
| Shelf Life (DMSO Stock) | 6 months at −80 °C (single-use aliquots; avoid repeated freeze-thaw) |
| Light Sensitivity | Moderate — flavonoids undergo photodegradation; amber glass vials supplied |
| Moisture Sensitivity | Hygroscopic at high humidity; store with desiccant; close container immediately after use |
6.2 Shipping & Regulatory Compliance
Air Freight & Express
FedEx, DHL, UPS available. Ambient shipping acceptable for powder; cold-chain (2–8 °C) available for large-volume or long-duration transit. Customs documentation included.
Sea Freight
Available for bulk orders (≥500 g). Temperature-controlled container recommended for tropical routes. Longer lead time; cost-effective for kilogram-scale procurement.
Packaging Options
Amber glass vials, HDPE containers, or aluminum-laminated foil bags with heat seal. Custom aliquot sizes available. Desiccant pack included in all packaging.
7. Frequently Asked Questions
Q: What is the difference between Oroxylin A and Baicalein?
Oroxylin A is the 6-O-methyl ether of Baicalein (i.e., Baicalein 6-methyl ether). The single methoxy group at C-6 is the critical structural difference — it confers increased lipophilicity (LogP 2.88 vs. ~2.4 for Baicalein), alters target selectivity (CDK9 and TKT inhibition are unique to Oroxylin A), and improves BBB penetration. Baicalein lacks dopamine reuptake inhibition and clinical-stage anticancer activity. For neuroscience applications requiring CNS penetration and DRI activity, Oroxylin A is the preferred compound; for broad-spectrum flavonoid antioxidant studies, Baicalein may suffice.
Q: What is the purity of your Oroxylin A, and how is it verified?
Our Oroxylin A is supplied at ≥99% purity as determined by HPLC-UV (area normalization, detection at 254 nm). Each batch is accompanied by a Certificate of Analysis (COA) documenting: HPLC chromatogram with retention time and purity, ¹H-NMR spectrum for structural identity confirmation, LC-MS for molecular weight verification, residual solvent analysis, and heavy metal testing. COAs are available upon request.
Q: Is Oroxylin A a controlled substance? Can I import it into my country?
No. Oroxylin A is not listed on any controlled substance schedule (DEA, UN, EU, or China NMPA narcotics lists). It is a naturally occurring flavonoid research compound and is freely importable for laboratory research use in the United States, European Union, United Kingdom, Canada, Australia, Japan, South Korea, and most other jurisdictions. However, researchers are responsible for verifying local import regulations. If your institution requires a specific import permit or end-use declaration, our logistics team can provide supporting documentation.
Q: What is the solubility of Oroxylin A for in vitro assays?
Oroxylin A is highly soluble in DMSO (≥30 mg/mL, ~105.5 mM). For in vitro experiments, we recommend: (1) dissolve in DMSO to prepare a concentrated stock (e.g., 50 mM); (2) dilute into culture medium to the desired working concentration (50–200 μM); (3) keep final DMSO concentration ≤0.1% v/v in cell culture to avoid solvent toxicity. For aqueous formulations without DMSO, cyclodextrin encapsulation or nano-suspension techniques may be required due to poor water solubility.
Q: What is the clinical trial status of Oroxylin A?
Oroxylin A has been approved by China's NMPA for a Phase I clinical trial in hepatocellular carcinoma (registration: ChiCTR2100051434). This trial is sponsored by China Pharmaceutical University and represents the first-in-human evaluation of Oroxylin A. The CDK9-TKT dual inhibition mechanism provides the scientific rationale. No clinical data are yet available from this trial, and Oroxylin A is not approved for any therapeutic indication by the FDA, EMA, or any other regulatory agency. Neuroscience applications remain entirely preclinical.
Q: How should I store Oroxylin A for long-term research use?
For powder: store at 2–8 °C in a tightly sealed, light-protected container with desiccant. Shelf life is ≥24 months under these conditions. For long-term storage (>6 months), −20 °C is recommended with argon or nitrogen purging. For DMSO stock solutions: aliquot into single-use volumes and store at −80 °C; avoid repeated freeze-thaw cycles which may cause precipitation or degradation. Oroxylin A is moderately light-sensitive; always use amber vials or foil wrapping.
Q: Can Oroxylin A cross the blood-brain barrier (BBB)?
Yes. Oroxylin A has a moderate LogP of 2.88, which is within the range favorable for passive BBB diffusion. The 6-methoxy substitution (absent in Baicalein) increases lipophilicity and CNS penetration. The compound's GABA-A NAM, dopamine reuptake inhibition, and BDNF upregulation effects in rodent brain tissue provide functional evidence of CNS exposure. However, oral bioavailability is limited by first-pass glucuronidation; researchers designing in vivo CNS studies should consider this pharmacokinetic limitation.
Q: What is the difference between Oroxylin A extracted from natural sources vs. synthetic?
Both natural extraction (from S. baicalensis root via high-speed counter-current chromatography, HSCCC) and chemical synthesis (methylation of Baicalein with dimethyl sulfate / K&sub2;CO&sub3; in acetone) yield chemically identical Oroxylin A. Our product is verified to ≥99% purity regardless of source. Synthetic routes may offer better batch-to-batch consistency and scalability; natural extraction may contain trace co-flavonoids if not adequately purified. All batches are verified by HPLC, NMR, and LC-MS to ensure identity and purity.
Q: Is Oroxylin A suitable as a reference standard for analytical method development?
Yes. The ≥99% HPLC purity, well-characterized UV absorption (λmax ~280 nm, typical for flavones), and availability of ¹H-NMR and LC-MS reference data make Oroxylin A suitable as a reference standard for analytical method development, quality control of botanical extracts, and quantification of Oroxylin A content in Scutellaria or Oroxylum preparations. Custom reference standard packaging with full characterization data package is available upon request.
Q: What documentation is provided with each order?
Standard documentation includes: Certificate of Analysis (COA) with HPLC purity, NMR, and LC-MS data; Commercial Invoice with harmonized tariff code; Packing List; and a Declaration of Non-Hazardous, Non-Controlled Status. Additional documents available upon request: GHS-compliant Safety Data Sheet (SDS/MSDS), Certificate of Origin, TSE/BSE statement, and residual solvent analysis. For institutional procurement requiring vendor qualification, we provide ISO certificates and quality management system documentation.
Q: Do you offer bulk or custom quantities for institutional research programs?
Yes. We supply Oroxylin A from 25 mg evaluation samples to kilogram-scale bulk orders. Tiered volume pricing is available for institutional accounts. Custom options include: dedicated batch reservation for longitudinal studies, custom aliquot packaging, sterile processing (gamma irradiation or aseptic filling), and formulation-grade micronization. Contact our procurement team with your specific requirements for a tailored quotation and lead time estimate.
Q: How does Oroxylin A compare to other natural product CDK inhibitors (e.g., Flavopiridol)?
Flavopiridol (Alvocidib) is a pan-CDK inhibitor (CDK1/2/4/7/9) with significant clinical toxicity (neutropenia, diarrhea, cytokine release syndrome). Oroxylin A shows preferential CDK9 inhibition with concentration-dependent efficacy and lower toxicity to normal cells (Wei et al., 2022). In normal hepatocyte L02 cells, Oroxylin A shows significantly less glycolytic suppression than in HepG2 cancer cells, suggesting a therapeutic window. However, no direct head-to-head clinical comparison exists, and Oroxylin A is at a much earlier development stage than Flavopiridol.
Ready to Advance Your Oroxylin A Research?
Whether you are investigating CDK9-mediated p53 restoration, TKT-dependent metabolic vulnerabilities, or GABA-A/BDNF-mediated neuroprotection, our ≥99% HPLC-grade Oroxylin A provides the purity and batch consistency your research demands. Supported by comprehensive analytical documentation, flexible packaging, and global logistics.
8. References (Selected)
- Wei L, et al. Novel CDK9 inhibitor oroxylin A promotes wild-type P53 stability and prevents hepatocellular carcinoma progression by disrupting both MDM2 and SIRT1 signaling. Acta Pharmacol Sin. 2022.
- Jia D, et al. Novel transketolase inhibitor oroxylin A suppresses the non-oxidative pentose phosphate pathway and hepatocellular carcinoma tumour growth in mice and patient-derived organoids. Clin Transl Med. 2022.
- Wei L, et al. Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1α destabilization. Cell Death Dis. 2015.
- Qiao C, et al. Oroxylin A modulates mitochondrial function and apoptosis in human colon cancer cells by inducing mitochondrial translocation of wild-type p53. Oncotarget. 2016.
- Zhao Y, et al. Oroxylin A promotes PTEN-mediated negative regulation of MDM2 transcription via SIRT3-mediated deacetylation to stabilize p53 and inhibit glycolysis in wt-p53 cancer cells. J Hematol Oncol. 2015.
- Jeon SJ, et al. Oroxylin A increases BDNF production by activation of MAPK-CREB pathway in rat primary cortical neuronal culture. Neurosci Res. 2011.
- Kim DH, et al. Oroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in mice. Brain Res Bull. 2014.
- Yoon SY, et al. Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro. Arch Pharm Res. 2013.
- Liao JF, et al. Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis root. Planta Med. 1998.
- Jeon SJ, et al. Oroxylin A induces BDNF expression on cortical neurons through adenosine A2A receptor stimulation: a possible role in neuroprotection. Biomol Ther. 2014.