NPASS Compound

Natural Product: NPC59215

Natural Product ID	NPC59215
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RSMQMCVBDYCRDI-VTAQJYJSSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	102580780
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0002207] O-glycosyl compounds

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 52 54 0 0 0 0 0 0 0 0999 V2000 -3.9775 2.9781 1.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7283 2.7167 1.2636 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2196 1.6794 0.3651 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2685 0.7980 -0.2626 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0671 1.5059 -1.3119 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4454 0.9992 -1.5346 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1105 0.5015 -0.4172 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4215 -0.2603 0.5135 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9242 -1.2450 1.1258 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0289 0.1245 0.7814 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4650 -0.1420 1.9428 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1491 0.2043 2.2049 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3124 0.7748 1.1907 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7864 -0.2607 0.4624 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5814 -0.3670 0.5210 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0653 -1.7093 1.0264 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7450 -2.5020 -0.0581 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9981 -1.6800 -0.4841 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6035 -0.2605 -0.4399 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3435 0.6760 -1.3073 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6759 0.7830 -1.1023 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7784 0.0423 -1.2641 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6941 -1.0991 -1.7514 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1653 0.4954 -0.8899 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1928 -0.1843 -0.7302 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9514 -2.0103 0.5017 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9829 -2.6705 -1.1875 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9675 -1.5369 2.0699 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8450 2.4545 1.1966 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2256 3.7982 2.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9700 3.3557 1.7408 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6516 2.1655 -0.4573 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6847 -0.0117 -0.8088 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4931 1.4766 -2.2833 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1049 2.5877 -1.0578 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0599 1.7659 -2.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3700 0.1460 -2.2717 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0816 -0.6503 2.6947 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5563 1.3835 1.7276 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9645 0.4452 1.1727 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2178 -2.3037 1.4593 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0707 -3.4573 0.3774 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3366 -2.0759 -1.4585 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7069 0.1015 0.6080 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1938 0.3049 -2.3780 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9005 1.7153 -1.2516 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8619 0.3461 -1.7307 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1464 1.5954 -0.6666 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5373 -0.0080 0.0049 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4321 -2.8120 0.1718 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3935 -2.2944 -2.0106 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4397 -2.3914 2.2427 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 19 25 1 0 18 26 1 0 17 27 1 0 16 28 1 0 13 3 1 0 25 15 1 0 10 4 1 0 1 29 1 0 1 30 1 0 2 31 1 0 3 32 1 6 4 33 1 6 5 34 1 0 5 35 1 0 6 36 1 0 6 37 1 0 11 38 1 0 13 39 1 1 15 40 1 1 16 41 1 1 17 42 1 1 18 43 1 6 19 44 1 1 20 45 1 0 20 46 1 0 24 47 1 0 24 48 1 0 24 49 1 0 26 50 1 0 27 51 1 0 28 52 1 0 M END

Standard InCHIKey	RSMQMCVBDYCRDI-VTAQJYJSSA-N
Standard InCHI	InChI=1S/C18H24O10/c1-3-9-10-4-5-24-16(23)11(10)6-26-17(9)28-18-15(22)14(21)13(20)12(27-18)7-25-8(2)19/h3,6,9-10,12-15,17-18,20-22H,1,4-5,7H2,2H3/t9-,10+,12-,13-,14+,15-,17+,18+/m1/s1
SMILES	C=C[C@@H]1[C@@H]2CCOC(=O)C2=CO[C@H]1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](COC(=O)C)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	400.14	Volume:	371.571 ? Van der Waals volume.
Dense:	1.077	LogP:	-0.386 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.044 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.132 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	20.0
TPSA:	140.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.388	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.695	Fsp³:	0.667
MCE-18:	53.333 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.53	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.053 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.219	Promiscuous compounds:	0.243

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.511	MDCK Permeability:	-4.946
Pgp-inhibitor:	0.028	Pgp-substrate:	0.229
PAMPA:	0.842 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.094
20% Bioavailability (F20%):	0.353	30% Bioavailability (F30%):	0.961
50% Bioavailability (F50%):	0.54

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.023	MRP1:	0.062
Plasma Protein Binding (PPB):	38.138%	Volume Distribution (VD):	-0.624
Fu:	63.68% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.0
BSEP inhibitor:	0.026

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.971
HLM stability:	0.78 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

2.146

Half-life (T1/2):

2.013

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.519	Drug-induced Liver Injury (DILI):	0.961
AMES Toxicity:	0.965	Rat Oral Acute Toxicity:	0.06
Maximum Recommended Daily Dose:	0.049	Skin Sensitization:	1.0
Carcinogencity:	0.584	Eye Corrosion:	0.0
Eye Irritation:	0.303	Respiratory Toxicity:	0.004
Drug-induced Neurotoxicity:	0.094	Ototoxicity:	0.834
Hematotoxicity:	0.538	Drug-induced Nephrotoxicity:	0.865
Genotoxicity:	0.762	RPMI-8226 Immunitoxicity:	0.102
A549 Cytotoxicity:	0.077	Hek293 Cytotoxicity:	0.078
BCF:	0.416 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.903 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.442 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.922 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO17857	Leptogorgia alba	Species	Gorgoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15844963]
NPO17857	Leptogorgia alba	Species	Gorgoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22647	Araucaria araucana	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13459	Nitraria tangutorum	Species	Nitrariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13459	Nitraria tangutorum	Species	Nitrariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22978	Morus tinctoria	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22978	Morus tinctoria	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13459	Nitraria tangutorum	Species	Nitrariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22647	Araucaria araucana	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22766	Lophanthus chinensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17857	Leptogorgia alba	Species	Gorgoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13459	Nitraria tangutorum	Species	Nitrariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22978	Morus tinctoria	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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	Organism Name	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

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC59215 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17414
0.1-0.2	28150
0.2-0.3	3935
0.3-0.4	268
0.4-0.5	71
0.5-0.6	15
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7667	Intermediate Similarity	NPC307699
0.6471	Remote Similarity	NPC472124
0.6377	Remote Similarity	NPC472126
0.6	Remote Similarity	NPC472125
0.5909	Remote Similarity	NPC117596
0.5667	Remote Similarity	NPC472131
0.5467	Remote Similarity	NPC284929
0.5395	Remote Similarity	NPC488456
0.5395	Remote Similarity	NPC488471
0.5395	Remote Similarity	NPC488466
0.5395	Remote Similarity	NPC488465
0.5395	Remote Similarity	NPC488460
0.5395	Remote Similarity	NPC488462
0.5333	Remote Similarity	NPC197541
0.5333	Remote Similarity	NPC118761
0.5309	Remote Similarity	NPC46641
0.5263	Remote Similarity	NPC267869
0.5211	Remote Similarity	NPC27687
0.5128	Remote Similarity	NPC86095

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC59215 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6188
0.1-0.2	2883
0.2-0.3	77
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
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
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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