PAC - CAS 2158322-33-7

PAC - CAS 2158322-33-7 Catalog number: BADC-00802

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PAC is a PROTAC with an ADC linker, intended to be conjugated to an antibody. PAC conjugated to an antibody is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).

Category
ADCs Cytotoxin with Linkers
Product Name
PAC
CAS
2158322-33-7
Catalog Number
BADC-00802
Molecular Formula
C94H107N13O16
Molecular Weight
1674.93
PAC

Ordering Information

Catalog Number Size Price Quantity
BADC-00802 -- $-- Inquiry
Description
PAC is a PROTAC with an ADC linker, intended to be conjugated to an antibody. PAC conjugated to an antibody is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).
IUPAC Name
N-[2-[2-[2-[2-[4-[(Z)-1-[4-[[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methoxy]phenyl]-2-phenylbut-1-enyl]phenoxy]ethyl-methylamino]-2-oxoethoxy]ethoxy]ethyl]-4-[(3S,4S)-7-cyano-1-[(2-methoxynaphthalen-1-yl)methyl]-4-methyl-3-[[(2S)-2-(methylamino)propanoyl]amino]-2-oxo-3,4-dihydro-1,5-benzodiazepine-5-carbonyl]benzamide
Canonical SMILES
CCC(=C(C1=CC=C(C=C1)OCCN(C)C(=O)COCCOCCNC(=O)C2=CC=C(C=C2)C(=O)N3C(C(C(=O)N(C4=C3C=C(C=C4)C#N)CC5=C(C=CC6=CC=CC=C65)OC)NC(=O)C(C)NC)C)C7=CC=C(C=C7)OCC8=CC=C(C=C8)NC(=O)C(CCCNC(=O)N)NC(=O)C(C(C)C)NC(=O)CCCCCN9C(=O)C=CC9=O)C1=CC=CC=C1
InChI
InChI=1S/C94H107N13O16/c1-9-74(65-19-12-10-13-20-65)85(68-34-41-73(42-35-68)123-58-63-25-37-71(38-26-63)100-90(114)77(23-18-47-99-94(96)118)101-91(115)86(60(2)3)102-81(108)24-14-11-17-49-105-82(109)45-46-83(105)110)67-32-39-72(40-33-67)122-52-50-104(7)84(111)59-121-54-53-120-51-48-98-89(113)69-28-30-70(31-29-69)92(116)107-62(5)87(103-88(112)61(4)97-6)93(117)106(78-43-27-64(56-95)55-79(78)107)57-76-75-22-16-15-21-66(75)36-44-80(76)119-8/h10,12-13,15-16,19-22,25-46,55,60-62,77,86-87,97H,9,11,14,17-18,23-24,47-54,57-59H2,1-8H3,(H,98,113)(H,100,114)(H,101,115)(H,102,108)(H,103,112)(H3,96,99,118)
InChIKey
AAGUYPGVVXJDLD-UHFFFAOYSA-N
Shipping
Room temperature
In Vitro
Treatment of HER2 expressing cells with HER2 antibody containing PAC Anti-HER2(Endox-XIAP) results in a marked decreased Estrogen Receptor-alpha (ERα) levels with an IC50 of 132 ng/mL. The PROTAC-Antibody Conjugate (PAC) molecules comprise an antibody conjugated via a linker (L1) to a PROTAC, wherein the PROTAC comprises an ubiquitin E3 ligase binding group ("E3LB"), a linker ("L2") and a protein binding group ("PB"). The following sections describe the components that comprise the PAC. To obtain a PAC having potent efficacy and a desirable therapeutic index, the following components are provided. 1. Antibody (Ab): The antibody portion of a PAC can target a cell that expresses an antigen whereby the antigen specific PAC is delivered intracellularly to the target cell, typically through endocytosis While PACs that comprise an antibody directed to an antigen that is not found on the cell surface may result in less specific intracellular delivery of the PROTAC portion into the cell, the PAC may still undergo pinocytosis. 2. Linkers (L1): A"linker" (L1) is a bifunctional or multifunctional moiety that can be used to link one or more PROTAC moieties (D) to an antibody (Ab) to form a PAC. In some embodiments, PACs can be prepared using a L1 having reactive functionalities for covalently attaching to the PROTAC and to the antibody. 3. PROTAC(D) .
In Vivo
Mean endoluminal penetration rates for the urothelium following PAC reached 149±61 μm (using 15 mg/50 ml). Doxorubicin penetration was significantly increased with higher drug concentration (15 vs. 3 mg/50 ml: p<0.01). PAC is a feasible minimally-invasive approach to the treatment of early-stage bladder cancer.
NCT NumberCondition Or DiseasePhaseStart DateSponsorStatus
NCT00222560Physical InactivityPhase 22007-04-30University of OttawaCompleted
NCT02355756Healthy VolunteersEarly Phase 12015-07-10Universitaire Ziekenhuizen LeuvenCompleted
NCT02964026Thoracic Surgery2017-02-17Vanderbilt UniversityCompleted
NCT02502383OverweightNot Applicable2020-11-09University of New MexicoCompleted
NCT01267097ObesityNot Applicable2014-02-20University of AlbertaCompleted
1. Linking AM-PAC Mobility and Daily Activity to the PROMIS Physical Function Metric
Anne Thackeray, Lan Yu, Robin Marcus, Janel Hanmer, Polly McCracken Phys Ther . 2021 Aug 1;101(8):pzab084. doi: 10.1093/ptj/pzab084.
Objective:The purpose of this study was to link Activity Measure for Post-Acute Care (AM-PAC) Mobility and Daily Activity scales to the PROMIS Physical Function (PF) allowing for a common metric across scales.Methods:Cross-sectional study of patients 18 years and older presenting to 1 of 8 outpatient rehabilitation clinics in southwestern Pennsylvania. Patients completed one survey with questions from the AM-PAC Daily Activity and Mobility short forms, and the PROMIS PF item bank. Using item response theory, 2 rounds of fixed-parameter calibration were performed. In the first, the AM-PAC Daily Activity and Mobility items were calibrated with 27 fixed item parameters from the PROMIS PF. Second, the AM-PAC Daily Activity items were calibrated with 11 PROMIS Upper Extremity fixed item parameters. This process uses the construct of physical function and equates AM-PAC items on the same underlying measurement scale for the PROMIS PF.Results:Both scales measured a wide range of functioning and demonstrated good calibration. Data were appropriate for a fixed-parameter item response theory-based crosswalk. AM-PAC Daily Activity and Mobility raw scores were mapped onto the PROMIS PF metric. AM-PAC Daily Activity scores were also mapped onto the PROMIS PF Upper Extremity metric.Conclusion:Question items from the AM-PAC Daily Activity, AM-PAC Mobility, and PROMIS PF similarly measure the construct of physical function. This consistency allows for a crosswalk of AM-PAC scores onto the PROMIS PF metric.Impact:Crosswalk tables developed in this study allow for converting scores from the AM-PAC Daily Activity and Mobility scales to the PROMIS PF metric. This will facilitate monitoring of longitudinal change in function over time and across settings.
2. CRC-Aided Adaptive BP Decoding of PAC Codes
Ming Jiang, Mingyang Zhu, Xianwen Zhang, Kailin Liu, Chunming Zhao Entropy (Basel) . 2022 Aug 22;24(8):1170. doi: 10.3390/e24081170.
Although long polar codes with successive cancellation decoding can asymptotically achieve channel capacity, the performance of short blocklength polar codes is far from optimal. Recently, Arıkan proposed employing a convolutional pre-transformation before the polarization network, called polarization-adjusted convolutional (PAC) codes. In this paper, we focus on improving the performance of short PAC codes concatenated with a cyclic redundancy check (CRC) outer code, CRC-PAC codes, since error detection capability is essential in practical applications, such as the polar coding scheme for the control channel. We propose an enhanced adaptive belief propagation (ABP) decoding algorithm with the assistance of CRC bits for PAC codes. We also derive joint parity-check matrices of CRC-PAC codes suitable for iterative BP decoding. The proposed CRC-aided ABP (CA-ABP) decoding can effectively improve error performance when partial CRC bits are used in the decoding. Meanwhile, the error detection ability can still be guaranteed by the remaining CRC bits and adaptive decoding parameters. Moreover, compared with the conventional CRC-aided list (CA-List) decoding, our proposed scheme can significantly reduce computational complexity, to achieve a better trade-off between the performance and complexity for short PAC codes.
3. Non-pharmacological remedies for post-viral acute cough
Giorgio Ciprandi, Maria Angela Tosca Monaldi Arch Chest Dis . 2021 Aug 10;92(1). doi: 10.4081/monaldi.2021.1821.
The post-viral acute cough (PAC) is a widespread symptom, mainly in childhood and adolescence, and is usually associated with an acute upper respiratory infection, namely the common cold. The use of cough relievers is, therefore, impressive, as documented by the market data. There are many medical devices and dietary supplements for treating PAC, which contain non-pharmacological components. Ancient people used traditional herbs to treat PAC. Thus, a well-established tradition considers natural remedies as an effective and safe way to relieve PAC. The herbal agents include polyphenols, flavonoids, saponins, glucosides, and alkaloids. Also, the European Medicine Agency has recognized the value of plant extracts and other natural substances to treat PAC. Nevertheless, a few studies investigated the role of non-pharmacologic remedies for PAC. There is some evidence for honey, glycerol, Althea officinalis, Drosera rotundifolia, Grindelia, Hedera helix, Pelargonium sidoides, Sambucus nigra, Thymus vulgaris, hyaluronic acid, and saline solutions. However, further rigorous studies should confirm natural products' efficacy and safety to relieve PAC.
The molarity calculator equation

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

The dilution calculator equation

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

This equation is commonly abbreviated as: C1V1 = C2V2

Historical Records: N3-PEG3-VC-PAB-MMAE | PAC
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