NPASS Compound

Natural Product: NPC104170

Natural Product ID	NPC104170
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	resokaempferol
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5281611
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0001136] Flavonols

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 30 32 0 0 0 0 0 0 0 0999 V2000 -2.0254 0.8425 1.1971 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2736 1.1003 1.6863 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3600 0.4348 1.2027 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1614 -0.4997 0.2116 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8887 -0.7704 -0.2952 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8108 -0.1119 0.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4355 -0.3017 -0.2600 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0441 -1.1712 -1.2195 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3037 -1.3147 -1.6100 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6301 -2.1305 -2.5029 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2239 -0.5285 -0.9727 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7860 0.3415 -0.0043 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5240 0.4229 0.3071 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7493 1.1271 0.6246 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0874 1.0515 0.3053 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5106 0.1727 -0.6696 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5674 -0.6093 -1.2983 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9954 1.8767 0.9845 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9469 -1.9757 -1.8786 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6162 0.7260 1.7275 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1677 1.3793 1.5905 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3964 1.8576 2.4826 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0116 -1.0312 -0.1778 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8014 -1.5079 -1.0648 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3648 1.8084 1.3905 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5740 0.1177 -0.9181 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8425 -1.3097 -2.0640 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6405 1.4637 1.6460 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7092 -2.9760 -1.9460 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1506 1.5154 1.3428 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 15 18 1 0 8 19 1 0 3 20 1 0 6 1 1 0 13 7 1 0 17 11 1 0 1 21 1 0 2 22 1 0 4 23 1 0 5 24 1 0 14 25 1 0 16 26 1 0 17 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	OBWHQJYOOCRPST-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)15-14(19)13(18)11-6-5-10(17)7-12(11)20-15/h1-7,16-17,19H
SMILES	C1=CC(=CC=C1C2=C(C(=O)C3=C(O2)C=C(C=C3)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	270.05	Volume:	265.186 ? Van der Waals volume.
Dense:	1.018	LogP:	2.073 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.098 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.828 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	90.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.632	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.179	Fsp³:	0.0
MCE-18:	17.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.784	Fluc inhibitor:	0.987 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.981 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.557 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.857	Promiscuous compounds:	0.915

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.621	MDCK Permeability:	-4.847
Pgp-inhibitor:	0.142	Pgp-substrate:	0.265
PAMPA:	0.774 ? 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):	0.038
20% Bioavailability (F20%):	0.317	30% Bioavailability (F30%):	0.781
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.738
Plasma Protein Binding (PPB):	96.659%	Volume Distribution (VD):	-0.699
Fu:	3.325% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.869
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.966
BSEP inhibitor:	0.83

ADMET: Metabolism

CYP1A2-inhibitor:	0.121	CYP1A2-substrate:	0.25
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.896
CYP2C9-inhibitor:	0.32	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.746	CYP2D6-substrate:	0.923
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.937 ? 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):

7.139

Half-life (T1/2):

1.493

ADMET: Toxicity

hERG Blockers:	0.105	hERG Blockers (10um):	0.508
Human Hepatotoxicity (H-HT):	0.403	Drug-induced Liver Injury (DILI):	0.673
AMES Toxicity:	0.552	Rat Oral Acute Toxicity:	0.454
Maximum Recommended Daily Dose:	0.742	Skin Sensitization:	0.629
Carcinogencity:	0.794	Eye Corrosion:	0.767
Eye Irritation:	0.998	Respiratory Toxicity:	0.639
Drug-induced Neurotoxicity:	0.108	Ototoxicity:	0.088
Hematotoxicity:	0.061	Drug-induced Nephrotoxicity:	0.026
Genotoxicity:	0.94	RPMI-8226 Immunitoxicity:	0.035
A549 Cytotoxicity:	0.203	Hek293 Cytotoxicity:	0.71
BCF:	1.218 ? 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:	3.751 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.404 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.071 ? 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
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	DOI[10.1039/C8GC03728K]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[20929806]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22544021]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22851214]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22909174]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23727191]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23864262]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[26062534]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[26358188]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[26488898]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[26951651]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29077207]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29096626]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[30061932]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[30496827]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[30684358]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[32830192]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[33195815]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[34824227]
NPO41850	A new engineered strain of Escherichia coli [n.a.]	Strain	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC104170 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	36170
0.1-0.2	11524
0.2-0.3	1736
0.3-0.4	325
0.4-0.5	79
0.5-0.6	14
0.6-0.7	6
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
0.8372	Intermediate Similarity	NPC51443
0.8372	Intermediate Similarity	NPC299379
0.7391	Intermediate Similarity	NPC74881
0.7347	Intermediate Similarity	NPC281207
0.6923	Remote Similarity	NPC602125
0.6731	Remote Similarity	NPC55205
0.6596	Remote Similarity	NPC172262
0.6538	Remote Similarity	NPC269652
0.6458	Remote Similarity	NPC116775
0.6	Remote Similarity	NPC195351
0.5962	Remote Similarity	NPC136840
0.5918	Remote Similarity	NPC93730
0.5686	Remote Similarity	NPC70136
0.566	Remote Similarity	NPC473042
0.56	Remote Similarity	NPC606557
0.549	Remote Similarity	NPC57601
0.5455	Remote Similarity	NPC143799
0.5385	Remote Similarity	NPC225731
0.5385	Remote Similarity	NPC20791
0.5283	Remote Similarity	NPC179271
0.5192	Remote Similarity	NPC187432
0.5179	Remote Similarity	NPC260895
0.5179	Remote Similarity	NPC605146
0.5094	Remote Similarity	NPC603556

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC104170 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6896
0.1-0.2	2199
0.2-0.3	45
0.3-0.4	9
0.4-0.5	0
0.5-0.6	1
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
0.5385	Remote Similarity	NPD1512	Phase 3

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