Pomalidomide-6-OH - ≥98% , CAS No.1547162-44-6

CAS: 1547162-44-6 Cat. No.: P1449952 Formula: C₁₃H₁₁N₃O₅ Molecular Weight: 289.24

GRADE & PURITY ≥98%

Storage

Store at 2-8°C

Shipped In

Wet ice

Overview

Pomalidomide-6-OH is the Pomalidomide-based cereblon (CRBN) ligand used in the recruitment of CRBN protein. Pomalidomide-6-OH can be connected to the ligand for protein by a linker to form PROTAC.

Specifications

Specifications & Purity

≥98%

Storage

Store at 2-8°C

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥98%

Names and Identifiers

Molecular Weight

289.24

Application Protocols

No tested applications or protocols are provided for this item.

• Recommended dilutions/assay setups: Not specified for this item; refer to CoA/Spec Sheet.

General research-only guidance (non-binding):

• Analytical standard preparation: Weigh accurately into a volumetric flask, dissolve in DMSO or MeOH to prepare a primary stock (e.g., 1.0 mg/mL), then prepare serial dilutions in 50:50 MeOH:water (0.1% formic acid) for LC–MS/MS calibration. Use low-bind vials.
• Cell-based assays: Pre-dissolve in DMSO to a high concentration; dilute into complete media ensuring final DMSO ≤0.5% v/v. Confirm solubility and absence of precipitation visually and by UV/LC.

For validated protocols or application notes, contact technical support with your SKU and lot number.

Biological Roles

Context (literature/general):

• Pomalidomide-6-OH represents a phase I oxidative metabolite of pomalidomide formed via aromatic hydroxylation. In biotransformation studies, phenolic metabolites often display altered polarity, plasma protein binding, and clearance relative to parent compounds.
• IMiD-class agents (thalidomide analogs) function as molecular glues that engage the cereblon (CRBN) E3 ubiquitin ligase complex (literature). Introduction of a phenolic OH can impact CRBN interaction and downstream neosubstrate recruitment in mechanistic assays, though behavior is context-dependent and should be empirically assessed.
• Conjugation potential: Phenolic metabolites frequently undergo phase II metabolism (glucuronidation/sulfation) in hepatocytes or microsomes, making the 6-OH species a useful standard for monitoring secondary metabolites.

Use in research workflows:

• Biomarker/metabolite identification in in vitro and in vivo sample sets.
• Calibration for quantitative bioanalysis (LC–MS/MS) including stability and recovery studies.
• Comparative mechanistic assays to parse the role of ring electronics and H-bonding in E3 ligase engagement (no claims of efficacy or safety; research only).

Note: Specific biological activity and potency of this metabolite are not established here. Not specified for this item; refer to primary literature and the product’s SDS/CoA for any additional characterization.

Buffer Applications

This product is not a buffering reagent. It does not define a classical buffer system or pH range.

Practical guidance:

• When formulating for biochemical assays, use standard buffers (e.g., PBS, HEPES, or phosphate-citrate) appropriate to your biology, and introduce Pomalidomide-6-OH via a concentrated DMSO stock followed by dilution into buffer.
• Verify compound stability in your selected buffer over the intended assay timescale, and monitor for adsorption to plastics; consider low-bind consumables.

Green Alternatives

Sustainability considerations relate mainly to solvent choice and work-up, as the compound identity is fixed.

Greener handling options (general guidance):

• Prefer ethanol or isopropanol over DMF/NMP when feasible for intermediate dissolution or cleaning steps, acknowledging potentially lower solubility.
• For preparative manipulations (derivatization), consider dimethyl carbonate, propylene carbonate, or 2-MeTHF as greener solvents where reaction compatibility allows.
• Use aqueous buffers with biobased solubilizers (cyclodextrins) to reduce DMSO content in biological assays.

Comparison (general; trade-offs):

• DMSO: High solvency; good EHS profile but may complicate waste streams.
• Ethanol: Renewable, low toxicity; may require warming/sonication for complete dissolution.
• 2-MeTHF: Greener ether for extractions/derivatizations; immiscible with water, facilitates separations but limited for final assay stocks.
• Propylene carbonate: Low volatility, good polarity; harder to remove, may not suit LC–MS sample prep.

Operational practices:

• Minimize solvent volumes through concentrated stocks and microscale workflows.
• Employ closed-vial dissolution and on-instrument dilution to reduce losses and exposure.
• Segregate halogenated vs non-halogenated solvent waste to enable improved downstream treatment.

Pharmaceutical Uses

Formulation/manufacturing context (non-clinical; no therapeutic claims):

• Pomalidomide-6-OH can serve as a reference standard in pharmaceutical R&D for analytical method development, impurity/metabolite profiling, and stability-indicating assays related to pomalidomide.
• It may be used to assess extraction recovery, matrix effects, and carryover in validated bioanalytical methods.
• No pharmacopeial monograph or excipient role is indicated for this item.

Regulatory note:

• Use is restricted to research and development. For GLP/GMP contexts, obtain and retain the lot-specific CoA including purity, identity methods, and storage conditions, and qualify the standard per internal SOPs (e.g., assign validity period, establish working standard from primary).

Item-specific statements:

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula/weight: Not specified for this item; refer to CoA/Spec Sheet.
• Storage: Store at 2–8°C; shipped on wet ice.

No clinical, diagnostic, or therapeutic use is intended or claimed.

Physical Properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/relevant; compound is typically a high-melting organic solid (general, literature expectation for IMiD analogs), but no item-specific value is provided.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Item-specific solubility is not provided. In general (literature/experience), pomalidomide analogs show:
  • Good solubility in polar aprotic solvents (DMSO, DMF, NMP).
  • Limited aqueous solubility at neutral pH; solubility may increase in basic media due to the phenolic OH deprotonation (literature expectation).
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet. Phenolic hydroxylation typically lowers logP relative to the parent (literature trend).
• pKa: Not specified for this item; refer to CoA/Spec Sheet. A phenolic OH often exhibits pKa in the ~8–10 range (general literature), but the local imide environment may modulate this; no item-specific value.
• Refractive index, UV cutoff, residuals: Not specified for this item; refer to CoA/Spec Sheet.

Note: For quantitative property requirements (e.g., exact solubility, spectral data), consult the lot-specific CoA and Technical/Spec Sheet.

Quality & Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Interpretation and guidance:

• For small-molecule library members and metabolite standards, suppliers commonly control identity by NMR and HRMS and assess purity by HPLC/UPLC (area %). Because no explicit grade or purity is listed here, refer to the CoA for the exact purity threshold and analytical methods used for this lot.
• Stabilizers/inhibitors: Not indicated for this item. If stabilizers are present, they will be declared on the CoA. Absence of such notation usually implies neat material or simple desiccant packaging, but confirm on the CoA.
• UV transparency/LC-MS suitability: Not specified for this item. If intended for analytical calibration, request chromatographic trace and impurity profile.
• Batch-to-batch considerations: IMiD analogs can show polymorphism or solvate formation depending on crystallization history. If your workflow is sensitive to solid form, request XRPD/DSC data.

Recommendations:

• Verify acceptance criteria (purity %, residual solvents, water content) in the lot-specific CoA prior to regulated use.
• For bioanalytical standards, prepare secondary working solutions immediately prior to use and verify response factors across lots to manage potential matrix effects.

Reaction & Applications

Research applications (non-clinical):

• Metabolite reference standard: 6-hydroxylated pomalidomide is a known oxidative metabolite (literature), useful for LC–MS/MS assay development, retention-time matching, and metabolite identification studies in drug metabolism and pharmacokinetics (DMPK) research.
• Enzymology: Substrate/product control in CYP-mediated biotransformation studies, phenotyping of oxidative pathways, and reaction phenotyping using recombinant isozymes or hepatocytes.
• SAR and E3 ligase binder chemistry: Hydroxylation on the isoindolinone ring alters electronics and hydrogen-bonding; used to probe cereblon-binding SAR and physicochemical impacts relative to the parent (literature/general in IMiD research).
• Analytical calibration: Preparation of standard curves, matrix-spike recovery assessments, and stability-indicating method validation.

Practical tips:

• Prepare fresh DMSO stocks and protect from light/moisture. The phenolic OH can undergo conjugation in biological matrices (e.g., glucuronidation/sulfation in vitro); include phase II inhibitors only if mechanistically justified for your study design.
• For LC–MS: Use acidic aqueous modifiers (0.1% FA) with MeCN to sharpen peaks; consider phenolic/imidic tautomerism when interpreting MS/MS fragments.
• Include internal standards (isotopically labeled if available) to control for adsorption to plastic and potential solution instability.

Note: This product is for research use only.

Reaction Conditions

Typical transformations of phenolic IMiD metabolites (general literature guidance; adjust to your substrate and scale):

• O-Alkylation (Williamson ether):

  • Reagents: Alkyl bromide/iodide or mesylate/tosylate; base: K2CO3 or Cs2CO3.
  • Solvent: DMF or acetone (anhydrous).
  • Conditions: 20–60°C, 2–18 h. Monitor by LC–MS. Avoid strong base to limit imide ring opening.

• Carbonate formation:

  • Reagents: CDI (1.1–1.5 eq), then ROH (1.2–2 eq) with catalytic DMAP; or use p-nitrophenyl chloroformate.
  • Solvent: DCM/THF/MeCN.
  • Conditions: 0–25°C initial activation, then 25–40°C coupling, 1–4 h.

• Mitsunobu etherification (for sterically hindered alkylation):

  • Reagents: DIAD/DEAD and PPh3 with the corresponding alcohol.
  • Solvent: THF or toluene.
  • Conditions: 0–25°C, 2–6 h. Note potential for competing N-alkylation; protect imide N if necessary.

• Esterification:

  • Reagents: Acyl chloride/anhydride with pyridine or DMAP.
  • Solvent: DCM or DMF.
  • Conditions: 0–25°C, 1–3 h.

Workup/purification:

• Quench carefully with aqueous buffer; avoid strong base. Purify by reversed-phase prep HPLC or silica gel using polar modifiers. Verify structure by 1H/13C NMR and HRMS.

These conditions are general literature practices; they are not item-specific specifications.

Safety & Handling

• GHS classification: Not specified for this item; refer to SDS.
• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-codes): Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General laboratory handling (professional guidance):

• Handle in a chemical fume hood; avoid inhalation of dust/particulate and contact with skin/eyes. Use appropriate PPE: lab coat, nitrile gloves, safety glasses.
• Avoid generating dust/aerosols. Use antistatic measures during weighing of fine powders.
• Incompatibilities: Strong oxidizers and strong bases/acids may cause degradation of the imide scaffold or phenolic functionality (general organic-chemistry caution). Avoid prolonged exposure to elevated temperatures and moisture.
• First aid (summary; defer to SDS): In case of contact, rinse affected area with water for 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. Seek medical attention for persistent symptoms.
• Waste: Collect organic solid/solution waste in designated containers; dispose of according to institutional and local regulations.
• Storage conditions (item-specific): Store at 2–8°C. Keep container tightly closed, protected from light and moisture. Shipped on wet ice.

Always consult the product SDS for authoritative hazard, toxicological, and first-aid information.

Solvent Selection

Compound class considerations:

• Pomalidomide-6-OH is an imide-containing, phenolic small molecule. Practical experience with related IMiD metabolites suggests good solubility in polar aprotic media and limited solubility in water at neutral pH (literature/general trends).

Recommended solvents and use-cases (general guidance):

• Primary stock preparation: DMSO (anhydrous) for 10–50 mM stocks; filter-sterilize if needed through PTFE. DMF or NMP are alternatives when DMSO is incompatible.
• Aqueous work: If aqueous delivery is required, pre-dissolve in DMSO, then dilute into buffered media with surfactant (e.g., 0.1% Tween 80) or cyclodextrins; avoid exceeding 0.5–1% DMSO in biological assays when possible.
• Basic media: Phenolic deprotonation in mild base (e.g., carbonate buffer) can increase apparent solubility (general phenomenon), but verify stability of the imide under basic conditions.
• Nonpolar solvents: Generally poor solubility expected; use only for extractions with phase-transfer strategies if necessary.

Comparison (general):

• DMSO: maximal solubility, broad compatibility; potential assay interference at high %.
• DMF/NMP: similar solvency; consider toxicity and removal challenges.
• MeOH/EtOH: moderate solubility; greener profile than DMF/NMP; volatility facilitates removal.

Always confirm solubility and stability empirically for your specific matrix.

Storage & Reconstitution

• Storage (item-specific): Store at 2–8°C. Shipments are on wet ice. Keep tightly closed, desiccated, and protected from light.
• Stability: Not specified for this item; refer to CoA/Spec Sheet for retest/expiry and any photostability or moisture-sensitivity notes.

Reconstitution and use (general guidance):

• Prepare concentrated stock solutions in dry DMSO (e.g., 10–50 mM) or MeOH immediately prior to use. Vortex and, if necessary, sonicate briefly. Filter through 0.2 µm PTFE to remove particulates when purity for analytical work is critical.
• For aqueous applications, add stock to buffer with vigorous mixing to avoid local supersaturation. Verify that no precipitation occurs upon dilution.
• Aliquot stocks into single-use vials to minimize freeze–thaw cycles. Store frozen aliquots at ≤−20°C if longer-term storage of solution is required (general practice), but confirm stability and adsorption losses for your matrix.
• Avoid repeated warming/cooling; use amber vials to limit light exposure.

Always defer to the lot-specific CoA and SDS for definitive storage limits, shelf life, and handling precautions.

Research Use: For research use only.

Structure & Identity

• SKU: P1449952
• Product name: Pomalidomide-6-OH
• CAS: 1547162-44-6
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general/literature description):

• Pomalidomide core (an IMiD scaffold) comprising an isoindoline-1,3-dione (phthalimide) fused imide ring linked to a 2,6-dioxopiperidin-3-yl (glutarimide) moiety (literature).
• The “6-OH” designation indicates a phenolic hydroxyl substituent on the isoindolinone/aromatic ring relative to the pomalidomide nucleus (literature), yielding a more polar phenolic metabolite compared to the parent.
• Functional groups: imide carbonyls (two in the isoindolinone and two in the glutarimide portion), a secondary amide-like imide N, and a phenolic OH (literature). The scaffold is overall neutral but includes multiple hydrogen-bond donors/acceptors.
• Stereochemistry: the glutarimide-bearing stereocenter in thalidomide-class scaffolds is typically racemic in many research materials unless otherwise specified; for this specific item, stereochemical specification is not provided. Not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Chemical reactivity considerations (general):

• Phenolic handle at the 6-position enables O-functionalization to access a suite of cereblon-ligand derivatives:
  • O-alkylation (Williamson ether synthesis) with alkyl halides or tosylates to tune lipophilicity and attach linkers.
  • Carbonate/carbamate formation using chloroformates or CDI + alcohols/amines to generate masked phenols and pro-moieties.
  • Esterification with acyl chlorides or acid anhydrides for modulatory groups.
• The dicarboximide motifs are relatively electrophilic and can be sensitive to strong nucleophiles/bases; mild conditions are preferred to preserve the scaffold.
• The aromatic ring offers potential for further functionalization via electrophilic substitution only under carefully controlled conditions due to deactivation by the imide carbonyls.

Value in medicinal chemistry and chemical biology (literature/general):

• Acts as a versatile intermediate for constructing CRBN-recruiting probes, heterobifunctional degraders, and immobilized ligands where an orthogonal linker is introduced at the phenol.
• The phenolic OH facilitates late-stage diversification, enabling SAR exploration around polarity and H-bonding while retaining the core binding pharmacophore.

Note: No item-specific reactivity data are provided; select conditions empirically and confirm integrity by LC–MS/NMR.

Target Specificity

No target specificity data (e.g., protein target, clone, isotype, species reactivity) are provided for this small-molecule product.

• Target specificity: Not specified for this item; refer to CoA/Spec Sheet and primary literature if using as a tool compound in target engagement assays.
• Note: As a metabolite standard, its primary use is analytical and mechanistic research rather than validated target-selective modulation.