NPASS Compound

Natural Product: NPC184939

Natural Product ID	NPC184939
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RSWKNNROTUMDID-GFCCVEGCSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones

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 34 36 0 0 0 0 0 0 0 0999 V2000 -2.7410 -1.0442 -1.2145 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0635 -1.1822 -0.7924 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4698 -0.6938 0.4115 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5442 -0.0596 1.2040 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2429 0.0797 0.7960 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7960 -0.4105 -0.4332 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3840 -0.2555 -0.8684 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1838 1.1247 -1.4119 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1333 1.6936 -1.1372 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3788 2.8711 -1.4661 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1889 0.9289 -0.4839 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5157 1.2888 -0.4949 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4896 0.5283 0.1424 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1424 -0.6256 0.8128 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8116 -0.9816 0.8208 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8306 -0.2234 0.1837 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5035 -0.5743 0.1890 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4540 -2.1372 1.4905 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1060 -1.3996 1.4570 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8452 2.4599 -1.1790 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9639 0.4359 2.4295 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7613 -0.8174 0.8463 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4738 -1.4512 -2.1800 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7692 -1.6885 -1.4428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5136 0.5717 1.4048 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1823 -0.9968 -1.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9835 1.8042 -1.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3685 1.0908 -2.5125 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5220 0.8215 0.1256 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1965 -2.9839 1.0113 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6161 -2.1467 1.0037 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7229 3.3599 -0.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4366 1.3319 2.5424 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5793 -0.7189 0.2424 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 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 15 18 1 0 14 19 1 0 12 20 1 0 4 21 1 0 3 22 1 0 6 1 1 0 17 7 1 0 16 11 1 0 1 23 1 0 2 24 1 0 5 25 1 0 7 26 1 6 8 27 1 0 8 28 1 0 13 29 1 0 18 30 1 0 19 31 1 0 20 32 1 0 21 33 1 0 22 34 1 0 M END

Standard InCHIKey	RSWKNNROTUMDID-GFCCVEGCSA-N
Standard InCHI	InChI=1S/C15H12O7/c16-7-2-1-6(3-8(7)17)12-5-10(19)13-9(18)4-11(20)14(21)15(13)22-12/h1-4,12,16-18,20-21H,5H2/t12-/m1/s1
SMILES	c1cc(c(cc1[C@H]1CC(=O)c2c(cc(c(c2O1)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	304.06	Volume:	285.403 ? Van der Waals volume.
Dense:	1.065	LogP:	1.819 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.014 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.452 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	127.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.402	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.201	Fsp³:	0.133
MCE-18:	61.471 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.804	Fluc inhibitor:	0.491 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.414 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.164 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.566	Promiscuous compounds:	0.153

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.539	MDCK Permeability:	-4.868
Pgp-inhibitor:	0.003	Pgp-substrate:	0.005
PAMPA:	0.418 ? 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):	0.011
20% Bioavailability (F20%):	0.884	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.963
Plasma Protein Binding (PPB):	96.506%	Volume Distribution (VD):	-0.571
Fu:	3.33% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.886
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.896
BSEP inhibitor:	0.014

ADMET: Metabolism

CYP1A2-inhibitor:	0.232	CYP1A2-substrate:	0.114
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.739
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.732
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.994
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.927
HLM stability:	0.968 ? 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):

15.417

Half-life (T1/2):

2.071

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.602
Human Hepatotoxicity (H-HT):	0.661	Drug-induced Liver Injury (DILI):	0.735
AMES Toxicity:	0.772	Rat Oral Acute Toxicity:	0.71
Maximum Recommended Daily Dose:	0.721	Skin Sensitization:	0.995
Carcinogencity:	0.256	Eye Corrosion:	0.098
Eye Irritation:	0.996	Respiratory Toxicity:	0.848
Drug-induced Neurotoxicity:	0.076	Ototoxicity:	0.699
Hematotoxicity:	0.077	Drug-induced Nephrotoxicity:	0.215
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.975	Hek293 Cytotoxicity:	0.379
BCF:	1.115 ? 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:	3.712 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.683 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.141 ? 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
NPO16807	Cyclamen purpurascens	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16807	Cyclamen purpurascens	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18126	Pojarkovia stenocephala	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16807	Cyclamen purpurascens	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11105	Cacalia floridana	Species	Asteraceae	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 NPC184939 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	23772
0.1-0.2	21437
0.2-0.3	3964
0.3-0.4	535
0.4-0.5	134
0.5-0.6	11
0.6-0.7	4
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
0.7143	Intermediate Similarity	NPC20354
0.6863	Remote Similarity	NPC321011
0.6863	Remote Similarity	NPC294852
0.6863	Remote Similarity	NPC188679
0.6735	Remote Similarity	NPC103991
0.5926	Remote Similarity	NPC192083
0.5556	Remote Similarity	NPC1612
0.5556	Remote Similarity	NPC183959
0.5455	Remote Similarity	NPC610021
0.537	Remote Similarity	NPC32441
0.537	Remote Similarity	NPC79943
0.537	Remote Similarity	NPC603284
0.5323	Remote Similarity	NPC480158
0.5263	Remote Similarity	NPC474208
0.5161	Remote Similarity	NPC610133
0.5147	Remote Similarity	NPC224851

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC184939 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4214
0.1-0.2	4824
0.2-0.3	102
0.3-0.4	5
0.4-0.5	3
0.5-0.6	2
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
0.5926	Remote Similarity	NPD2393	Clinical (unspecified phase)
0.537	Remote Similarity	NPD1552	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