NPASS Compound

Structure

NPC473703 OpenBabel07101719502D 46 50 0 0 1 0 0 0 0 0999 V2000 5.8188 -4.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9528 -7.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6848 -1.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5379 -0.0003 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2405 -4.2837 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2434 -1.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5509 -2.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9757 1.4311 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8188 -5.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2207 -1.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4887 -4.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2207 -4.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9528 -6.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8188 -1.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6369 -0.4342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0223 -3.6602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0868 -1.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3547 -1.8303 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4887 -3.3303 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2207 -3.3303 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0868 -2.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7521 -1.1031 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1152 -1.5374 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4887 -1.3303 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6227 -2.8303 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9528 -1.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5793 -1.2029 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9528 -3.3303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6945 -0.3345 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8188 -2.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0576 -2.3060 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0868 -5.8303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4887 -5.3303 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6227 -1.8303 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3547 -2.8303 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -1.9532 -4.0256 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9528 -0.3303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4055 -1.7662 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9528 -4.3303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5207 0.2289 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2207 -6.3303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6848 -3.3303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0747 0.9972 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0868 -4.8303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8733 -2.6714 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 9 1 0 0 0 0 2 13 1 0 0 0 0 3 14 1 0 0 0 0 4 15 1 0 0 0 0 5 16 1 0 0 0 0 6 35 1 0 0 0 0 7 43 1 0 0 0 0 8 44 1 0 0 0 0 9 13 2 0 0 0 0 10 17 1 0 0 0 0 10 18 1 0 0 0 0 11 19 1 0 0 0 0 11 34 3 0 0 0 0 12 20 1 0 0 0 0 12 45 1 0 0 0 0 13 33 1 0 0 0 0 14 26 1 0 0 0 0 14 30 2 0 0 0 0 15 27 1 0 0 0 0 15 31 2 0 0 0 0 16 37 2 0 0 0 0 16 46 1 0 0 0 0 17 21 2 0 0 0 0 17 26 1 0 0 0 0 18 24 1 0 0 0 0 18 36 1 6 0 0 0 19 25 1 0 0 0 0 19 36 1 1 0 0 0 20 21 1 0 0 0 0 20 36 1 6 0 0 0 21 28 1 0 0 0 0 22 23 2 0 0 0 0 22 29 1 0 0 0 0 23 27 1 0 0 0 0 23 32 1 0 0 0 0 24 22 1 6 0 0 0 24 35 1 0 0 0 0 25 32 1 0 0 0 0 25 35 1 1 0 0 0 26 38 2 0 0 0 0 27 39 2 0 0 0 0 28 30 1 0 0 0 0 28 40 2 0 0 0 0 29 31 1 0 0 0 0 29 41 2 0 0 0 0 30 43 1 0 0 0 0 31 44 1 0 0 0 0 32 46 1 1 0 0 0 33 42 2 0 0 0 0 33 45 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	633.23
Volume:	623.16
LogP:	4.028
LogD:	2.29
LogS:	-3.503
# Rotatable Bonds:	7
TPSA:	182.25
# H-Bond Aceptor:	13
# H-Bond Donor:	4
# Rings:	5
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.161
Synthetic Accessibility Score:	5.878
Fsp3:	0.364
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.383
MDCK Permeability:	1.5437168258358724e-05
Pgp-inhibitor:	0.769
Pgp-substrate:	0.961
Human Intestinal Absorption (HIA):	0.985
20% Bioavailability (F20%):	0.928
30% Bioavailability (F30%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012
Plasma Protein Binding (PPB):	90.03567504882812%
Volume Distribution (VD):	1.141
Pgp-substrate:	11.93376636505127%

ADMET: Metabolism

CYP1A2-inhibitor:	0.01
CYP1A2-substrate:	0.25
CYP2C19-inhibitor:	0.086
CYP2C19-substrate:	0.351
CYP2C9-inhibitor:	0.898
CYP2C9-substrate:	0.937
CYP2D6-inhibitor:	0.073
CYP2D6-substrate:	0.114
CYP3A4-inhibitor:	0.305
CYP3A4-substrate:	0.927

ADMET: Excretion

Clearance (CL):	2.959
Half-life (T1/2):	0.728

ADMET: Toxicity

hERG Blockers:	0.045
Human Hepatotoxicity (H-HT):	0.883
Drug-inuced Liver Injury (DILI):	0.981
AMES Toxicity:	0.102
Rat Oral Acute Toxicity:	0.893
Maximum Recommended Daily Dose:	0.602
Skin Sensitization:	0.802
Carcinogencity:	0.054
Eye Corrosion:	0.003
Eye Irritation:	0.027
Respiratory Toxicity:	0.792

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC473703

Natural Product ID:	NPC473703
*Common Name:**	XMMINTFMKAOIKZ-BISUAZHOSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	XMMINTFMKAOIKZ-BISUAZHOSA-N
Standard InCHI:	InChI=1S/C33H35N3O10/c1-9-13(2)33(42)45-12-20-21-17(26(38)14(3)30(43-7)28(21)40)10-18-24-22-23(27(39)15(4)31(44-8)29(22)41)32(46-16(5)37)25(35(24)6)19(11-34)36(18)20/h9,18-20,24-25,32H,10,12H2,1-8H3/b13-9-/t18-,19-,20-,24-,25+,32-/m0/s1
SMILES:	CC=C(C)C(=O)OCC1C2=C(CC3N1C(C4C(C5=C(C3N4C)C(=O)C(=C(C5=O)C)OC)OC(=O)C)C#N)C(=O)C(=C(C2=O)OC)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL449646
PubChem CID:	11331116
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0002567] Isoquinoline quinones

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11908959]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Caledonian	n.a.	PMID[1453184]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Thai	n.a.	PMID[14640515]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	thai	n.a.	PMID[15217287]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1710256]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	coral reef habitat at a depth of approximately 20 m from the sea bed surface, at Sangalaki, Indonesia (2 04 59 N, 118 23 41 E)	1996-MAR	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesia	n.a.	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[31260310]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Philippine	n.a.	PMID[7473578]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7798966]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	120.0	nM	PMID[520656]
NPT3558	Cell Line	QG-56		IC50	=	300.0	nM	PMID[520656]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC473703 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	164
0.1-0.2	1277
0.2-0.3	8977
0.3-0.4	23547
0.4-0.5	8228
0.5-0.6	484
0.6-0.7	13
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC239252
0.9593	High Similarity	NPC97861
0.9531	High Similarity	NPC25025
0.9286	High Similarity	NPC161644
0.7259	Intermediate Similarity	NPC315110
0.7133	Intermediate Similarity	NPC313348
0.7133	Intermediate Similarity	NPC475987
0.6892	Remote Similarity	NPC473955
0.6763	Remote Similarity	NPC13351
0.6358	Remote Similarity	NPC82129
0.6309	Remote Similarity	NPC120335
0.6222	Remote Similarity	NPC133420
0.6181	Remote Similarity	NPC230849
0.6148	Remote Similarity	NPC469895
0.6133	Remote Similarity	NPC215507
0.6098	Remote Similarity	NPC475342
0.6081	Remote Similarity	NPC309525
0.6015	Remote Similarity	NPC241426
0.599	Remote Similarity	NPC475180
0.5931	Remote Similarity	NPC174463
0.5909	Remote Similarity	NPC120420
0.5888	Remote Similarity	NPC473746
0.5871	Remote Similarity	NPC99864
0.5822	Remote Similarity	NPC471673
0.5816	Remote Similarity	NPC298484
0.5792	Remote Similarity	NPC44040
0.5789	Remote Similarity	NPC173173
0.5789	Remote Similarity	NPC478136
0.5781	Remote Similarity	NPC296589
0.5779	Remote Similarity	NPC316401
0.5779	Remote Similarity	NPC315011
0.5778	Remote Similarity	NPC472167
0.5755	Remote Similarity	NPC87919
0.5743	Remote Similarity	NPC11379
0.5714	Remote Similarity	NPC307165
0.5714	Remote Similarity	NPC200412
0.5714	Remote Similarity	NPC93179
0.5714	Remote Similarity	NPC120599
0.5714	Remote Similarity	NPC156336
0.5706	Remote Similarity	NPC321485
0.5706	Remote Similarity	NPC477519
0.5706	Remote Similarity	NPC327517
0.5706	Remote Similarity	NPC317377
0.5706	Remote Similarity	NPC319334
0.5706	Remote Similarity	NPC322372
0.5704	Remote Similarity	NPC21324
0.5696	Remote Similarity	NPC45813
0.5695	Remote Similarity	NPC469999
0.5674	Remote Similarity	NPC271562
0.5664	Remote Similarity	NPC195435
0.5664	Remote Similarity	NPC196073
0.5662	Remote Similarity	NPC472162
0.5652	Remote Similarity	NPC471699
0.5649	Remote Similarity	NPC315387
0.5649	Remote Similarity	NPC316205
0.5646	Remote Similarity	NPC211215
0.5643	Remote Similarity	NPC44514
0.5643	Remote Similarity	NPC75523
0.563	Remote Similarity	NPC150041
0.5629	Remote Similarity	NPC318445
0.5629	Remote Similarity	NPC316133
0.5629	Remote Similarity	NPC314629
0.5625	Remote Similarity	NPC47857
0.5625	Remote Similarity	NPC168758
0.5625	Remote Similarity	NPC181510
0.5621	Remote Similarity	NPC247902
0.5621	Remote Similarity	NPC262880
0.5616	Remote Similarity	NPC272166
0.5615	Remote Similarity	NPC130436
0.5615	Remote Similarity	NPC469860
0.5615	Remote Similarity	NPC469861
0.5608	Remote Similarity	NPC106791
0.5608	Remote Similarity	NPC235625
0.5608	Remote Similarity	NPC201889
0.56	Remote Similarity	NPC23963

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC473703 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	121
0.1-0.2	805
0.2-0.3	3465
0.3-0.4	3798
0.4-0.5	911
0.5-0.6	47
0.6-0.7	2
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7259	Intermediate Similarity	NPD7196	Clinical (unspecified phase)
0.6148	Remote Similarity	NPD2259	Approved
0.6148	Remote Similarity	NPD2258	Approved
0.5935	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5871	Remote Similarity	NPD8415	Approved
0.5867	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.5779	Remote Similarity	NPD2101	Approved
0.5714	Remote Similarity	NPD8392	Approved
0.5714	Remote Similarity	NPD8390	Approved
0.5714	Remote Similarity	NPD8391	Approved
0.5667	Remote Similarity	NPD8080	Discontinued
0.5658	Remote Similarity	NPD8273	Phase 1
0.5652	Remote Similarity	NPD8384	Approved
0.5629	Remote Similarity	NPD7642	Approved
0.5616	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.56	Remote Similarity	NPD8274	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data