2. Stem Cell/Wnt
  3. Hedgehog
  4. MEDI-5304

MEDI-5304 is a hedgehog antibody inhibitor with human sonic hedgehog (SHH) KD of 5.13 pmol/L, and human Indian hedgehog (IHH) KD of 34.7 pmol/L. MEDI-5304 binds and neutralizes SHH and IHH, blocks downstream target gene transcription, inhibits osteoblast differentiation. MEDI-5304 can be used for the research of colon cancer.

For research use only. We do not sell to patients.

MEDI-5304

MEDI-5304 Chemical Structure

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MEDI-5304 Related Antibodies

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Description

MEDI-5304 is a hedgehog antibody inhibitor with human sonic hedgehog (SHH) KD of 5.13 pmol/L, and human Indian hedgehog (IHH) KD of 34.7 pmol/L. MEDI-5304 binds and neutralizes SHH and IHH, blocks downstream target gene transcription, inhibits osteoblast differentiation. MEDI-5304 can be used for the research of colon cancer[1].

Species Reactivity

Human
In Vitro

MEDI-5304 (16 h) binds recombinant human SHH and human/mouse IHH, but not DHH, in an in vitro ELISA assay[1].
MEDI-5304 (24 h) dose-dependently inhibits SHH- and IHH-induced activation of the mGLI1 luciferase reporter in NIH 3T3 cells[1].
MEDI-5304 (72 h) dose-dependently inhibits SHH- and IHH-induced osteoblast differentiation of C3H10T1/2 cells[1].
MEDI-5304 (24 h) dose-dependently inhibits SHH- and IHH-induced upregulation of the hedgehog target gene mGLI1 in C3H10T1/2 cells[1].
MEDI-5304 (4 days) does not inhibit tumorsphere formation from patient-derived P479 and 947 pancreatic cancer cells in vitro[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

MEDI-5304 Related Antibodies
Parmacokinetics
Species Dose Route Cmax Tmax
Mice[1] 1 mg/kg i.p. 8000 ng/mL 4 h
In Vivo

MEDI-5304 (0.03-10 mg/kg; i.p.; single dose) inhibits paracrine hedgehog signaling in Colo205 xenograft stroma with a maximum 90% reduction in mouse GLI1 mRNA levels at doses of 1 mg/kg and above[1].
MEDI-5304 (0.1-10 mg/kg; i.p.; twice weekly for 5 weeks) exhibits single-agent antitumor activity in the HT-29/MEF paracrine signaling model at doses of 1 mg/kg and above, and enhances Carboplatin (HY-17393)-mediated tumor growth inhibition[1].
MEDI-5304 (10-30 mg/kg; i.p.; twice weekly) does not inhibit tumor growth or alter CSC frequency in primary pancreatic adenocarcinoma xenograft models[1].
MEDI-5304 (10-50 mg/kg; i.p.; two doses on day 0 and day 7; 2 weeks) causes mild odontodysplasia in rat incisors at a dose of 50 mg/kg, with no other observed toxic effects[1].
MEDI-5304 (0.3-75 mg/kg; i.v.; weekly for 3 weeks) is well tolerated in cynomolgus monkeys across tested doses, with measurable pharmacodynamic effects in skin via reduced hedgehog target gene expression and no observed toxic effects[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: NCr nude (athymic, female)[1]
Dosage: 0.03 mg/kg; 0.1 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: i.p.; single dose
Result: Decreased mouse GLI1 mRNA levels by approximately 90% and mouse PTC1 mRNA levels by about 75% in tumor stroma 24 hours after dosing at 1 mg/kg and above.
Reached a maximum of nearly 8 mg/mL at 4 hours, decayed to undetectable levels by day 7, and inhibited mouse GLI1 and PTC1 mRNA levels for at least 72 hours following a single 1 mg/kg i.p. dose.
Showed no effect on mouse GLI1 and PTC1 mRNA levels at doses below 1 mg/kg.
Animal Model: NCr nude (athymic, female)[1]
Dosage: 0.1 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: i.p.; twice weekly
Result: Statistically significantly inhibited tumor growth (P < 0.05) relative to control antibody on day 35 at doses of 1 mg/kg and above.
Caused dramatic inhibition of stromal hedgehog target gene transcripts (mouse GLI1, GLI2, PTC1, PTC2, HHIP, IGFBP5) but had no effect on mouse GLI3 or SMO at doses that inhibited tumor growth.
Significantly reduced mouse GLI1 mRNA levels in mouse skin at doses of 1 mg/kg and above.
Showed no efficacy at the 0.1 mg/kg dose.
Resulted in significantly greater tumor growth inhibition (P < 0.05) than either agent alone when combined with Carboplatin.
Animal Model: Rag2 knockout (female); NOD/SCID (male, 8-week-old)[1]
Dosage: 10 mg/kg; 30 mg/kg
Administration: i.p.; twice weekly
Result: Showed no single-agent antitumor activity in subcutaneous P479, orthotopic 890, and orthotopic 947 pancreatic models.
Did not enhance gemcitabine-mediated tumor growth inhibition in any of the three pancreatic models.
Had no effect on CSC frequency (defined as ESA+, CD44+, CD24+ cells) in any of the three pancreatic models.
Decreased stromal mouse GLI1 levels by >90% in all models.
Animal Model: Rat[1]
Dosage: 10 mg/kg; 50 mg/kg
Administration: i.p.; two doses on day 0 and day 7; 2 weeks
Result: Had no effect on appearance, behavior, body weights, hematology, coagulation, or clinical chemistry parameters.
Caused odontodysplasia of incisor teeth in the 50 mg/kg group, characterized by loss of odontoblast cell layer polarity and deposits of dentin-like material.
Animal Model: Cynomolgus monkey[1]
Dosage: 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg; 75 mg/kg
Administration: i.v.; single initial dose; weekly for 3 weeks
Result: Showed no changes in clinical signs, body weights, or clinical pathology parameters (including Troponin I, Troponin T, or creatine kinase isozymes).
Decreased GLI1, PTCH1, and PTCH2 mRNA levels in skin punch biopsies on day 4 at all doses.
Gene ID

6469  [NCBI]

Accession

Q15465
Target

SHH/Hedgehog
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.
Formulation

Please refer to the lot-specific COA for specific buffer information.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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MEDI-5304 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MEDI-5304MEDI5304MEDI 5304Hedgehoghedgehog pathwaycolon cancerhuman SHHhuman/mouse IHHstromal cellsNIH 3T3 cellsC3H10T1/2 cellsmouse SHHpancreatic cancerosteoblast differentiationInhibitorinhibitorinhibit

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