NPASS Compound

Natural Product: NPC479406

Natural Product ID	NPC479406
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NMMKAWLUUWRFRP-RECXWPGBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71563062
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 55 58 0 0 0 0 0 0 0 0999 V2000 -0.4983 -0.2524 -3.2110 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3967 -0.2045 -2.1199 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9586 -0.1153 -0.8145 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3817 -0.0691 -0.5234 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8506 0.0204 0.7764 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0643 0.0658 1.8333 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4008 0.0189 1.5288 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8702 -0.0715 0.2149 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2347 -0.1120 0.0233 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6796 -0.1935 -1.1540 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1255 -0.0663 1.0752 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5673 0.0231 2.3431 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2692 0.0609 2.5143 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5762 -0.1079 0.8937 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2591 -1.2965 0.8764 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6328 -1.2405 0.6992 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2972 -0.0372 0.5449 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5784 1.1299 0.5679 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2120 1.1083 0.7422 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4987 2.2977 0.7633 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.6714 0.0288 0.3670 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1761 0.0679 1.0955 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2929 0.0411 0.2732 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0846 1.3273 0.3812 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3696 1.2905 -0.3781 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0926 -0.0237 -0.2794 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1390 -1.1842 -0.3705 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8485 -2.5108 -0.2813 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9095 -2.5929 -1.1799 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0897 -1.0769 0.5050 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0068 -0.0885 -1.3210 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2112 2.2901 0.0634 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3171 2.3770 -0.1014 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0226 -0.6071 -4.1380 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0367 0.7131 -3.4380 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3073 -0.9988 -3.0125 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0903 -0.1050 -1.3569 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3142 0.1355 2.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2423 0.0614 3.2019 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7114 -2.2180 0.9995 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1992 -2.1561 0.6807 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0520 2.0918 0.4519 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5275 2.3306 1.0212 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0517 0.7885 -0.1802 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9806 -0.0304 -0.7830 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2949 1.5322 1.4626 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1244 1.5131 -1.4519 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6554 -0.1271 0.6574 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6976 -1.1424 -1.4099 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1809 -3.3622 -0.5085 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2457 -2.5895 0.7617 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6725 -3.0062 -0.7316 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8918 0.6326 -1.9723 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1392 2.4934 1.0152 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2696 3.1462 0.4880 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 11 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 17 21 1 0 5 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 27 30 1 0 26 31 1 0 25 32 1 0 24 33 1 0 8 3 1 0 19 14 1 0 30 23 1 0 13 7 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 6 38 1 0 12 39 1 0 15 40 1 0 16 41 1 0 18 42 1 0 20 43 1 0 21 44 1 0 23 45 1 6 24 46 1 1 25 47 1 6 26 48 1 1 27 49 1 6 28 50 1 0 28 51 1 0 29 52 1 0 31 53 1 0 32 54 1 0 33 55 1 0 M END

Standard InCHIKey	NMMKAWLUUWRFRP-RECXWPGBSA-N
Standard InCHI	InChI=1S/C22H22O11/c1-30-14-5-10(32-22-21(29)20(28)19(27)16(7-23)33-22)6-15-17(14)18(26)12(8-31-15)11-3-2-9(24)4-13(11)25/h2-6,8,16,19-25,27-29H,7H2,1H3/t16-,19-,20+,21-,22-/m1/s1
SMILES	COc1cc(cc2c1c(=O)c(co2)c1ccc(cc1O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.12	Volume:	430.443 ? Van der Waals volume.
Dense:	1.074	LogP:	0.556 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.112 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.992 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	179.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.302	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.974	Fsp³:	0.318
MCE-18:	86.966 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.539	Fluc inhibitor:	0.249 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.771 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.735 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.095	Promiscuous compounds:	0.345

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.282	MDCK Permeability:	-5.285
Pgp-inhibitor:	0.0	Pgp-substrate:	0.123
PAMPA:	0.979 ? 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):	0.608
20% Bioavailability (F20%):	0.164	30% Bioavailability (F30%):	0.95
50% Bioavailability (F50%):	0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.14
Plasma Protein Binding (PPB):	78.884%	Volume Distribution (VD):	-0.083
Fu:	21.867% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.508
BSEP inhibitor:	0.005

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.035
HLM stability:	0.003 ? 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):

2.065

Half-life (T1/2):

4.298

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.148
Human Hepatotoxicity (H-HT):	0.652	Drug-induced Liver Injury (DILI):	0.831
AMES Toxicity:	0.865	Rat Oral Acute Toxicity:	0.046
Maximum Recommended Daily Dose:	0.116	Skin Sensitization:	0.985
Carcinogencity:	0.336	Eye Corrosion:	0.0
Eye Irritation:	0.498	Respiratory Toxicity:	0.046
Drug-induced Neurotoxicity:	0.015	Ototoxicity:	0.869
Hematotoxicity:	0.141	Drug-induced Nephrotoxicity:	0.586
Genotoxicity:	0.917	RPMI-8226 Immunitoxicity:	0.119
A549 Cytotoxicity:	0.336	Hek293 Cytotoxicity:	0.531
BCF:	0.447 ? 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:	3.169 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.576 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.735 ? 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
NPO16444	Apios americana	Species	Fabaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[29932657]
NPO16444	Apios americana	Species	Fabaceae	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	1000.0	nM	PMID[29932657]

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 NPC479406 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	23290
0.1-0.2	22811
0.2-0.3	2690
0.3-0.4	845
0.4-0.5	183
0.5-0.6	26
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.84	Intermediate Similarity	NPC479402
0.8267	Intermediate Similarity	NPC100720
0.7468	Intermediate Similarity	NPC80140
0.7407	Intermediate Similarity	NPC479407
0.7037	Intermediate Similarity	NPC479401
0.6374	Remote Similarity	NPC479403
0.6265	Remote Similarity	NPC234739
0.619	Remote Similarity	NPC610763
0.6118	Remote Similarity	NPC138540
0.6071	Remote Similarity	NPC197896
0.6071	Remote Similarity	NPC105511
0.6071	Remote Similarity	NPC313163
0.6071	Remote Similarity	NPC161749
0.593	Remote Similarity	NPC205076
0.5814	Remote Similarity	NPC73511
0.5647	Remote Similarity	NPC45165
0.5618	Remote Similarity	NPC229729
0.5517	Remote Similarity	NPC258035
0.5517	Remote Similarity	NPC156457
0.5465	Remote Similarity	NPC135345
0.5455	Remote Similarity	NPC121527
0.5395	Remote Similarity	NPC162680
0.5333	Remote Similarity	NPC307938
0.5333	Remote Similarity	NPC481043
0.5326	Remote Similarity	NPC48773
0.5287	Remote Similarity	NPC183357
0.5217	Remote Similarity	NPC307518
0.5217	Remote Similarity	NPC607201
0.5208	Remote Similarity	NPC479405
0.519	Remote Similarity	NPC90665
0.5165	Remote Similarity	NPC169404
0.5165	Remote Similarity	NPC176186
0.5165	Remote Similarity	NPC224462
0.5155	Remote Similarity	NPC479404
0.5056	Remote Similarity	NPC259070
0.5056	Remote Similarity	NPC211014
0.5056	Remote Similarity	NPC348541
0.5055	Remote Similarity	NPC182045
0.5055	Remote Similarity	NPC599850

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479406 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5629
0.1-0.2	3442
0.2-0.3	64
0.3-0.4	12
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
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
0.6071	Remote Similarity	NPD4381	Clinical (unspecified phase)

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