Payload Information

General Information of This Payload
Payload ID
PAY0EJBOG
Name
IRDye 700DX
Synonyms
Irdye 700DX; Irdye 700dx NHS ester; C51A2YUX4N; UNII-C51A2YUX4N; 916821-46-0; Silicate(4-), (2,5-dioxo-1-pyrrolidinyl 6-(((3-((29H,31H-phthalocyanin-1-yl-kappaN29,kappaN30,kappaN31,kappaN32)oxy)propoxy)carbonyl)amino)hexanoato(2-))bis(N-(3-((hydroxy-kappaO)dimethylsilyl)propyl)-3-sulfo-N,N-bis(3-sulfopropyl)-1-propanamin; SILICATE(4-), (2,5-DIOXO-1-PYRROLIDINYL 6-(((3-((29H,31H-PHTHALOCYANIN-1-YL-.KAPPA.N29,.KAPPA.N30,.KAPPA.N31,.KAPPA.N32)OXY)PROPOXY)CARBONYL)AMINO)HEXANOATO(2-))BIS(N-(3-((HYDROXY-.KAPPA.O)DIMETHYLSILYL)PROPYL)-3-SULFO-N,N-BIS(3-SULFOPROPYL)-1-PROPANAMINIUMATO(4-))-, SODIUM (1:4), (OC-6-13)-
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Structure
Formula
C74H96N12Na4O27S6Si3
Isosmiles
C[Si](C)(CCC[N+](CCCS(=O)(=O)[O-])(CCCS(=O)(=O)[O-])CCCS(=O)(=O)[O-])O[Si]1(N2C3=C4C=CC=CC4=C2N=C5C6=C (C=CC=C6OCCCOC(=O)NCCCCCC(=O)ON7C(=O)CCC7=O)C(=N5)N=C8N1C(=NC9=NC(=N3)C1=CC=CC=C19)C1=CC=CC =C18)O[Si](C)(C)CCC[N+](CCCS(=O)(=O)[O-])(CCCS(=O)(=O)[O-])CCCS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+]
PubChem CID
102004325
InChI
InChI=1S/C74H100N12O27S6Si3.4Na/c1-120(2,52-21-42-85(36-15-46-114(91,92)93,37-16-47-115(94,95)96)38-17-48-116(97,98)99)112-122(113-121(3,4)53-22-43-86(39-18-49-117(100,101)102,40-19-50-118(103,104)105)41-20-51-119(106,107)108)83-70-56-26-9-10-27-57(56)72(83)80-68-60-30-14-31-61(109-44-23-45-110-74(90)75-35-13-5-6-32-64(89)111-82-62(87)33-34-63(82)88)65(60)69(77-68)81-73-59-29-12-11-28-58(59)71(84(73)122)79-67-55-25-8-7-24-54(55)66(76-67)78-70;;;;/h7-12,14,24-31H,5-6,13,15-23,32-53H2,1-4H3,(H5-2,75,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108);;;;/q;4*+1/p-4
InChIKey
NTBCSBGVMJMABW-UHFFFAOYSA-J
IUPAC Name
tetrasodium;3-[3-[[38-[dimethyl-[3-[tris(3-sulfonatopropyl)azaniumyl]propyl]silyl]oxy-12-[3-[[6-(2,5-dioxopyrrolidin-1-yl)oxy-6-oxohexyl]carbamoyloxy]propoxy]-9,18,27,36,37,39,40,41-octaza-38-siladecacyclo[17.17.3.110,17.128,35.02,7.08,37.011,16.020,25.026,39.029,34]hentetraconta-1,3,5,7,9,11(16),12,14,17(41),18,20,22,24,26,28(40),29,31,33,35-nonadecaen-38-yl]oxy-dimethylsilyl]propyl-bis(3-sulfonatopropyl)azaniumyl]propane-1-sulfonate
Pharmaceutical Properties
Molecule Weight
1954.2
Polar area
606
Complexity
4240
xlogp Value
.
Heavy Count
126
Rot Bonds
44
Hbond acc
29
Hbond Donor
1
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Cell survival rate 83.4 %
U87EGFR-Luc cells
Glioblastoma
CVCL_0022 
[1]
Cell survival rate 85.2 %
K562 cells
Chronic myeloid leukemia
CVCL_0004 
[1]
Cell survival rate 86.7 %
SK-OV-3-Luc cells
Ovarian serous cystadenocarcinoma
CVCL_4Y20 
[2]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
RM-1995 [Phase 1 (discontinued)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Key eligibility: Adults (≥18) with platinum-refractory HNSCC/cuSCC having accessible superficial lesions (≤1cm depth), measurable disease (RECIST 1.1), ECOG 0-2. Major exclusions: recent anticancer therapies (2 weeks/5 half-lives), active infections (HIV/HBV/HCV), QTc-prolonging medications, uncontrolled comorbidities, or hypersensitivity to antibody components. Tumor specimens required for pathology confirmation.

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Administration Dosage
RM-1995 will be administered by intravenous (IV) infusion followed approximately 24 hours later by tumor illumination with 690 nm non thermal red light using the PIT690 Laser System. The starting dose of RM-1995 will be 0.25 mg/kg and escalated up to 2.0 mg/kg over 6 dosing cohorts
Related Clinical Trial
NCT Number NCT05220748  Phase Status PHASE1
Clinical Description
A Phase 1 First-in-Human, Drug-dose Escalation Study of RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced Cutaneous Squamous Cell Carcinoma or With Head and Neck Squamous Cell Carcinoma
Primary Endpoint
Primary endpoints focus on safety evaluation (DLTs, AEs) and dose determination (MTD/MAD) for RM-1995 PIT monotherapy (Phase 1a) and combination therapy with pembrolizumab (Phase 1b) over 24 months in recurrent HNSCC/cuSCC patients.
Other Endpoint
Secondary objectives include PK analysis (RM-1995, total antibody, IR-700 concentrations) during treatment cycles and antitumor activity assessment (ORRPIT by RECIST 1.1/irRECIST) over 24 months.
Experiment 2 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT05220748  Phase Status Phase 1
Clinical Description
A phase 1 first-in-human, drug-dose escalation study of RM-1995 photoimmunotherapy, as monotherapy or combined with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma or with head and neck squamous cell carcinoma.
CTLA4-IR700 [Investigative]
 ADC Info 
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 38% Positive CTLA4 expression (CTLA4 +++/++)
Method Description
Mice with tumors reaching approximately 50-100 mm3 in volume were used for the experiments. Mice were monitored each day and tumor volume (length x width2 x 0.5) was measured twice a week until the tumor volume reached 2,000 mm3.
In Vivo Model Oropharyngeal cancer PDX model (PDX: mEERL-hEGFR)
ARB102-IR700 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 36.97% High CDH17 expression (CDH17 +++)
Method Description
The tumor-bearing mice were subjected to three cycles of PIT treatment, once per week.
In Vivo Model SNU-C1 CDX model
In Vitro Model Colon adenocarcinoma SNU-C1 cells CVCL_1708
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 37.92% High CDH17 expression (CDH17 +++)
Method Description
The tumor-bearing mice were subjected to three cycles of PIT treatment, once per week.
In Vivo Model LoVo CDX model
In Vitro Model Colon adenocarcinoma LoVo cells CVCL_0399
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 53.65% High CDH17 expression (CDH17 +++)
Method Description
The tumor-bearing mice were subjected to three cycles of PIT treatment, once per week.
In Vivo Model AsPC-1 CDX model
In Vitro Model Pancreatic ductal adenocarcinoma AsPC-1 cells CVCL_0152
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 58.37% High CDH17 expression (CDH17 +++)
Method Description
The tumor-bearing mice were subjected to three cycles of PIT treatment, once per week.
In Vivo Model AsPC-1 CDX model
In Vitro Model Pancreatic ductal adenocarcinoma AsPC-1 cells CVCL_0152
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.12 ug/mL
High CDH17 expression (CDH17 +++)
Method Description
GI cancer cells were treated with PIT and cell viability was measured by MTT assay to determine EC50. Data is presented as mean SEM (n=3).
In Vitro Model Colon adenocarcinoma LoVo cells CVCL_0399
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Effective Concentration (EC50)
49 ug/mL
High CDH17 expression (CDH17 +++)
Method Description
GI cancer cells were treated with PIT and cell viability was measured by MTT assay to determine EC50. Data is presented as mean SEM (n=3).
In Vitro Model Colon adenocarcinoma SW480 cells CVCL_0546
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Effective Concentration (EC50)
74 ug/mL
High CDH17 expression (CDH17 +++)
Method Description
GI cancer cells were treated with PIT and cell viability was measured by MTT assay to determine EC50. Data is presented as mean SEM (n=3).
In Vitro Model Colon adenocarcinoma SNU-C1 cells CVCL_1708
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Effective Concentration (EC50)
86 ug/mL
High CDH17 expression (CDH17 +++)
Method Description
GI cancer cells were treated with PIT and cell viability was measured by MTT assay to determine EC50. Data is presented as mean SEM (n=3).
In Vitro Model Pancreatic ductal adenocarcinoma AsPC-1 cells CVCL_0152
TROP2-IR700 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 49.50% Positive TROP2 expression (TROP2+++/++)
Method Description
Five million of PK59 or TFK1 cells were injected subcutaneously into the right dorsum of the mice. Five million of 3T3/HER2 cells were injected subcutaneously into the left dorsum of the mice as negative control. The dose of ADC was 200 ug TROP2-IR700.
In Vivo Model PK59 CDX model
In Vitro Model Pancreatic carcinoma PK-59 cells CVCL_4897
Tra-IR700 [Clinical candidate]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 54.50% Negative HER2 expression (HER2 -)
Method Description
Tra-IR700 (3.6 ug/g) or T-DM1-IR700 (3.6 ug/g) was administered intravenously to mice on Day 1 (with NIR light 6 days after tumor cell transplantation). The dose similar to that of T-DM1 administered to humans (3.6 mg/kg). The NIR-light was irradiated at 1 and 2 days after the drug administration.
In Vivo Model MDA-MB-468GFP CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468GFP cells CVCL_DH83
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.80% Negative HER2 expression (HER2 -)
Method Description
Tra-IR700 (3.6 ug/g) or T-DM1-IR700 (3.6 ug/g) was administered intravenously to mice on Day 1 (with NIR light 6 days after tumor cell transplantation). The dose similar to that of T-DM1 administered to humans (3.6 mg/kg). The NIR-light was irradiated at 1 and 2 days after the drug administration.
In Vivo Model MDA-MB-468GFP CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468GFP cells CVCL_DH83
AU-011 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 55.55%
Method Description
C57BL/6-albino mice were subcutaneously inoculated with 5x105 MC38 on the right flank. Once the tumors had reached an average volume of approximately 125 mm3 as determined by measuring with a caliper, the mice were randomly divided into groups after which 100 g AU-011 in 100 uL was administered intravenously into the tail vein or intraperitoneally, or 30 g AU-011 in 30 L was administered intratumorally.

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In Vivo Model MC38 CDX model
In Vitro Model Mouse colon adenocarcinoma MC-38 cells CVCL_B288
ICAM-1-IR700 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 63.22% High ICAM-1 expression (ICAM-1+++)
Method Description
Female homozygote athymic nude mice, 6-8 weeks old, MDA-MB-468-luc (4x106) or MDA-MB-231 (1x106) cells were inoculated into the right dorsum of mice. ICAM-1-IR700 (100 g) was injected 9 and 25days after cell inoculation, respectively (day 1). The mice were killed with CO2 when the tumor volume reached 2000 mm3.

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 2 Reporting the Activity Date of This ADC [10]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.40% High ICAM-1 expression (ICAM-1+++)
Method Description
Female homozygote athymic nude mice, 6-8 weeks old, MDA-MB-468-luc (4x106) or MDA-MB-231 (1x106) cells were inoculated into the right dorsum of mice. ICAM-1-IR700 (100 g) was injected 9 and 25days after cell inoculation, respectively (day 1). The mice were killed with CO2 when the tumor volume reached 2000 mm3.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
References
Ref 1 Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers. Sci Rep. 2018 May 25;8(1):8126.
Ref 2 Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer. Mol Cancer Ther. 2015 Jan;14(1):141-50.
Ref 3 RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced CuSCC and HNSCC
Ref 4 A Phase 1 First-in-Human, Drug-dose Escalation Study of RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced Cutaneous Squamous Cell Carcinoma or With Head and Neck Squamous Cell Carcinoma, NCT05220748
Ref 5 Simultaneously Combined Cancer Cell- and CTLA4-Targeted NIR-PIT Causes a Synergistic Treatment Effect in Syngeneic Mouse Models. Mol Cancer Ther. 2021 Nov;20(11):2262-2273. doi: 10.1158/1535-7163.MCT-21-0470. Epub 2021 Sep 13.
Ref 6 Cadherin-17 Targeted Near-Infrared Photoimmunotherapy for Treatment of Gastrointestinal Cancer. Mol Pharm. 2020 Oct 5;17(10):3941-3951. doi: 10.1021/acs.molpharmaceut.0c00700. Epub 2020 Sep 24.
Ref 7 Photoimmunotherapy targeting biliary-pancreatic cancer with humanized anti-TROP2 antibody. Cancer Med. 2019 Dec;8(18):7781-7792. doi: 10.1002/cam4.2658. Epub 2019 Nov 1.
Ref 8 Near-infrared-induced drug release from antibody-drug double conjugates exerts a cytotoxic photo-bystander effect. Bioeng Transl Med. 2022 Aug 21;7(3):e10388. doi: 10.1002/btm2.10388. eCollection 2022 Sep.
Ref 9 Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate induces complete responses in a murine model of local and distant tumors. Cancer Immunol Immunother. 2023 Jul;72(7):2405-2422. doi: 10.1007/s00262-023-03425-3. Epub 2023 Mar 30.
Ref 10 Intercellular adhesion molecule-1-targeted near-infrared photoimmunotherapy of triple-negative breast cancer. Cancer Sci. 2022 Sep;113(9):3180-3192.