DAPT (Synonyms: GSI-IX)

Name: DAPT
Brand: MedChemExpress
SKU: HY-13027
Rating: 5.0 (111 reviews)

Cat. No.: HY-13027 Purity: 99.97%: FAQs
Data Sheet SDS COA Handling Instructions

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DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

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

DAPT Chemical Structure

CAS No. : 208255-80-5

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 74	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 74	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 67	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 115	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 355	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 496	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Based on 111 publication(s) in Google Scholar

Other Forms of DAPT:

DAPT (GMP) Get quote

99 Publications Citing Use of MCE DAPT

IHC

Proliferation Assay

: DAPT purchased from MedChemExpress. Usage Cited in: Ecotoxicol Environ Saf. 2022 Oct 19;246:114183. [Abstract]; Detection of cell viability after treatment with different concentrations of DAPT (5 μM, 10 μM, 15 μM, 20 μM; for 24 h).

: DAPT purchased from MedChemExpress. Usage Cited in: Ecotoxicol Environ Saf. 2022 Oct 19;246:114183. [Abstract]; DAPT treatment enhances the protein expression of Bax and decreases the expression of Bcl2. And the expression of cleaved-caspase3 is upregulated after DAPT treatment (10 μM; for 24 h).

: DAPT purchased from MedChemExpress. Usage Cited in: Neural Regen Res. 2019 Mar;14(3):452-461. [Abstract]; Western blot assay for Hes1 (left) and Hes5 (right) protein expression in the right prefrontal cortex of cerebral I/R mice following DAPT treatment.

: DAPT purchased from MedChemExpress. Usage Cited in: Biomed Pharmacother. 2018 Nov;107:1370-1376. [Abstract]; ECa109 and EC9706 cells are treated with concentrations of GSI-DAPT (0, 10 and 20 μM) for 48 h. The expressions of Notch3, DTX1 and Hes1 are investigated by Western blotting.

: DAPT purchased from MedChemExpress. Usage Cited in: Biomed Pharmacother. 2018 Nov;107:1370-1376. [Abstract]; ECa109 and EC9706 cells are treated with concentrations of GSI-DAPT (0, 10 and 20 μM) for 48 h. The expressions of LSD1 and H3K4me2 are investigated by Western blotting.

: DAPT purchased from MedChemExpress. Usage Cited in: Int J Cancer. 2018 Aug 1;143(3):645-656. [Abstract]; Evaluation of expression change of Notch downstream under the androgen-deprived condition with or without the treatment of DAPT by western blot assay.

: DAPT purchased from MedChemExpress. Usage Cited in: J Cell Physiol. 2018 Mar;233(3):2225-2237. [Abstract]; DAPTprevents Nicd splitting from Notch1 and has been recognized as a Notch1 pathway inhibitor. Treatment with DAPT also inhibits the expression of Col IV and FN, resembling the effect of Notch1 siRNA.

: DAPT purchased from MedChemExpress. Usage Cited in: Drug Des Devel Ther. 2018 Nov 8;12:3847-3854. [Abstract]; Western anslysis of protein analysis of NOX2, NICD, Hes1, Hes5 in the treatment of TBI, TBI+vehicle, TBI+DAPT and TBI+DPI, respectively.

: DAPT purchased from MedChemExpress. Usage Cited in: J Cell Biochem. 2018 Oct 26;120(2):1903-1915. [Abstract]; The distribution of aggrecan is increased in the DAPT group.

: DAPT purchased from MedChemExpress. Usage Cited in: PLoS One. 2018 Feb 15;13(2):e0193037. [Abstract]; After DAPT treatment, the protein levels of Notch, Hes1 and Hes5 are downregulated in severe injury group. After DAPT treatment, the protein levels of Bcl-2 are upregulated while those of Bax, caspase-3 and caspase-9 are downregulated.

: DAPT purchased from MedChemExpress. Usage Cited in: World J Gastroenterol. 2017 Apr 7;23(13):2330-2336. [Abstract]; Notch γ-secretase inhibitor attenuates notch and transforming growth factor-β signaling pathways in peripheral blood mononuclear cells of liver fibrosis rats. Western blot analysis of protein expression of Notch1, Hes1, Hes5, TGF-β and Smad3 and quantification in PBMCs (2 × 10⁶) from rats treated with DAPT or DMSO for 24 h.

: DAPT purchased from MedChemExpress. Usage Cited in: Department Medicine. Yale University. 2016 Jan.; Treatment with DAPT does not markedly alter expression of p27^Kip1 in bulk or CD133^- cells, but dramatically enhances its expression in CD133⁺ cells.

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Biological Activity
Protocol
Purity & Documentation
References
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Description

IC₅₀ & Target

IC50: 115 nM (Aβ), 200 nM (Aβ42)^[5]

Cellular Effect

Cell Line	Type	Value	Description	References
Hep 3B2	IC₅₀	5 μM Compound: DAPT	Cytotoxicity against human Hep3B cells assessed as growth inhibition after 72 hrs by SRB assay Cytotoxicity against human Hep3B cells assessed as growth inhibition after 72 hrs by SRB assay	[PMID: 30108693]
Huh-7	IC₅₀	5 μM Compound: DAPT	Cytotoxicity against human HuH7 cells assessed as growth inhibition after 72 hrs by SRB assay Cytotoxicity against human HuH7 cells assessed as growth inhibition after 72 hrs by SRB assay	[PMID: 30108693]
Mahlavu	IC₅₀	5 μM Compound: DAPT	Cytotoxicity against human Mahlavu cells assessed as growth inhibition after 72 hrs by SRB assay Cytotoxicity against human Mahlavu cells assessed as growth inhibition after 72 hrs by SRB assay	[PMID: 30108693]
SNU-475	IC₅₀	0.6 μM Compound: DAPT	Cytotoxicity against human SNU475 cells assessed as growth inhibition after 72 hrs by SRB assay Cytotoxicity against human SNU475 cells assessed as growth inhibition after 72 hrs by SRB assay	[PMID: 30108693]

In Vitro

DAPT inhibits Aβ production over 90%, effects only a modest reduction in APPβ in the culture media. Although APPβ is reduced by about 30% by DAPT treatment, this effect is not concentration-dependent and is reversed by the removal of DAPT^[1].
CNE-2 cells are treated with increasing concentrations of DAPT (0, 25, 50 and 75 μM), and the γ-secretase-generated Notch 1 fragment Val1744-NICD is decreased after 48 h in a dose-dependent manner (P<0.01). The activation of γ-secretase is almost completely inhibited by DAPT at the concentration of 50 μM^[3].

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

In Vivo

DAPT is administered to PDAPP mice (100 mg/kg s.c.) and the levels of DAPT and Aβ are examined in the brain cortex. Peak DAPT levels of 490 ng/g are achieved in the brain 3 h after treatment, and levels greater than 100 ng/g (~200 nM) are sustained throughout the first 18 h. These brain concentrations of DAPT are in excess of its IC₅₀ for lowering Aβ in neuronal cultures (115 nM), and results in a robust and sustains pharmacodynamic effect^[1].
DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Western blot analyses also show a significant decrease of Notch 1 and NF-κB expression in DAPT (0.03 mg/kg) group (P<0.05 vs. MCAO group)^[2].

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

Molecular Weight

432.46

Formula

C₂₃H₂₆F₂N₂O₄

CAS No.

208255-80-5

Appearance

Solid

Color

White to off-white

SMILES

FC1=CC(F)=CC(CC(N[C@H](C(N[C@H](C(OC(C)(C)C)=O)C2=CC=CC=C2)=O)C)=O)=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 62.5 mg/mL (144.52 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Ethanol : 10 mg/mL (23.12 mM; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3124 mL	11.5618 mL	23.1235 mL
5 mM	0.4625 mL	2.3124 mL	4.6247 mL
10 mM	0.2312 mL	1.1562 mL	2.3124 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 3

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.78 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 4

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 5

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 6

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 7

Add each solvent one by one: 10% EtOH 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1 mg/mL (2.31 mM); Clear solution

This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: Corn Oil
Solubility: 10 mg/mL (23.12 mM); Suspended solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 15% Cremophor EL 85% Saline
Solubility: 20 mg/mL (46.25 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.97%

Select Batch:

Data Sheet (282 KB) SDS (393 KB)

COA (246 KB) HNMR (258 KB) RP-HPLC (245 KB) LCMS (96 KB) Elemental Analysis Report (104 KB)

Handling Instructions (2659 KB)

References

[1]. Dovey HF, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173-81. [Content Brief]

[2]. Li S, et al. DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and nuclear factor κB in rats. Neurol Sci. 2012 Dec;33(6):1257-64. [Content Brief]

[3]. Zhou JX, et al. γ-secretase inhibition combined with NSC 119875 enhances apoptosis of nasopharyngeal carcinoma cells.Exp Ther Med. 2012 Feb;3(2):357-361. [Content Brief]

[4]. Tanimizu N, et al. Intrahepatic bile ducts are developed through formation of homogeneous continuous luminal network and its dynamic rearrangement in mice. Hepatology. 2016 Jul;64(1):175-88. [Content Brief]

[5]. Michael T. Chang, et al. Notch Drives Proliferation And Radiation Resistance Of Cancer Stem Cells In Adenoid Cystic Carcinoma. Yale University. January 2016.

[6]. Majumder S, et al. Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease. J Clin Invest. 2018 Jan 2;128(1):483-499. [Content Brief]

[7]. Yixin Tao, et al. β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis. J Mol Cell Biol. 2018 May 16. [Content Brief]

Cell Assay ^[1]	Human embryonic kidney cells, transfected with the gene for APP₇₅₁ (HEK 293) are used for routine Aβ reduction assays. Cells are plated in 96-well plates and allowed to adhere overnight in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum. Cells are pre-treated for 2 h at 37°C with DAPT (0, 0.4, 2, 10, 50 and 250 nM), media are aspirated off and fresh compound solutions applied. After an additional 2-h treatment period, conditioned media are drawn off and analyzed by a sandwich ELISA (266-3D6) specific for total Aβ. Reduction of Aβ production is measured relative to control cells treated with 0.1% DMSO and expressed as a percentage inhibition. Data from at least six doses in duplicate are fitted to a four-parameter logistical model using XLfit software in order to determine potency^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]^[3]	Mice^[1] The three- to four-month-old heterozygous PDAPP transgenic mice overexpressing the APP_V717F mutant form of the amyloid precursor protein. Each treatment group (n=10) consists of equal numbers of age-matched male and female animals that are fasted overnight prior to treatment. Both treatment and control groups are dosed at a volume of 10 mL/kg with DAPT or vehicle alone. Tissues are processed and all Aβ and APP measurements are made. After removal of the brain, the cortex from one hemisphere is homogenized, centrifuged, and the supernatant is used for Aβ measurements. Cortex from the other hemisphere is snap frozen for analysis of compound levels. Aβ levels are expressed as ng/g of wet tissue weight, and percentage reductions are calculated relative to the mean Aβ level of tissue from vehicle-treated control animals. Data are analyzed with Mann-Whitney non-parametric statistics to assess significance. Rats^[3] Male Sprague-Dawley rats (260-290 g) are used. DAPT solution is stereotactically injected into the lateral cerebral ventricle (LV) immediately after MCAO. The stereotactic injections into the LVs are performed at coordinates −0.8 mm anteroposterior, ±1.5 mm mediolateral and −4.5 mm dorsoventral from the bregma. 30 rats are randomly assigned to three operating groups (10 rats in each group): sham-operated group that receive equal volume of PBS without MCAO operation; MCAO group that receive equal volume PBS after MCAO (MCAO); and DAPT group that receive DAPT as 0.03 mg/kg after MCAO. 24 h after operation the first neurological function is assessed and then 48 h after operation the second neurological function is assessed. Meanwhile, brain water content and infarction volume are measured and compared among different groups. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Dovey HF, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173-81. [Content Brief] [2]. Li S, et al. DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and nuclear factor κB in rats. Neurol Sci. 2012 Dec;33(6):1257-64. [Content Brief] [3]. Zhou JX, et al. γ-secretase inhibition combined with NSC 119875 enhances apoptosis of nasopharyngeal carcinoma cells.Exp Ther Med. 2012 Feb;3(2):357-361. [Content Brief] [4]. Tanimizu N, et al. Intrahepatic bile ducts are developed through formation of homogeneous continuous luminal network and its dynamic rearrangement in mice. Hepatology. 2016 Jul;64(1):175-88. [Content Brief] [5]. Michael T. Chang, et al. Notch Drives Proliferation And Radiation Resistance Of Cancer Stem Cells In Adenoid Cystic Carcinoma. Yale University. January 2016. [6]. Majumder S, et al. Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease. J Clin Invest. 2018 Jan 2;128(1):483-499. [Content Brief] [7]. Yixin Tao, et al. β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis. J Mol Cell Biol. 2018 May 16. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

Ethanol / DMSO	1 mM	2.3124 mL	11.5618 mL	23.1235 mL	57.8088 mL
	5 mM	0.4625 mL	2.3124 mL	4.6247 mL	11.5618 mL
	10 mM	0.2312 mL	1.1562 mL	2.3124 mL	5.7809 mL
	15 mM	0.1542 mL	0.7708 mL	1.5416 mL	3.8539 mL
	20 mM	0.1156 mL	0.5781 mL	1.1562 mL	2.8904 mL
DMSO	25 mM	0.0925 mL	0.4625 mL	0.9249 mL	2.3124 mL
	30 mM	0.0771 mL	0.3854 mL	0.7708 mL	1.9270 mL
	40 mM	0.0578 mL	0.2890 mL	0.5781 mL	1.4452 mL
	50 mM	0.0462 mL	0.2312 mL	0.4625 mL	1.1562 mL
	60 mM	0.0385 mL	0.1927 mL	0.3854 mL	0.9635 mL
	80 mM	0.0289 mL	0.1445 mL	0.2890 mL	0.7226 mL
	100 mM	0.0231 mL	0.1156 mL	0.2312 mL	0.5781 mL

DAPT Related Classifications

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:

DAPT208255-80-5GSI-IXOrganoidγ-secretaseAmyloid-βAutophagyNotchApoptosisGamma secretaseβ-amyloid peptideAβAbetaInhibitorinhibitorinhibit

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DAPT (Synonyms: GSI-IX)

Customer Review

Other Forms of DAPT:

DAPT Related Antibodies

99 Publications Citing Use of MCE DAPT

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

DAPT Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

DAPT Related Classifications

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