NPASS Compound

Natural Product: NPC191660

Natural Product ID	NPC191660
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KITUBOBTRYFYBY-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5315116
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 45 48 0 0 0 0 0 0 0 0999 V2000 -4.6500 1.5495 -0.4279 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7139 0.4165 -0.3027 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3395 0.7698 0.1818 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3515 0.9242 1.6734 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7329 1.9436 -0.5274 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5657 -0.4523 -0.2425 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2734 -0.9992 -1.2908 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7662 -2.1495 -1.8703 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5966 -2.7124 -1.4033 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0900 -2.1280 -0.3398 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3236 -2.7013 0.1716 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8868 -3.6087 -0.4476 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8707 -2.1669 1.4398 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6435 -0.6840 1.5651 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5206 0.1210 0.6789 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2998 1.4936 0.5589 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0804 2.2837 -0.2509 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1132 1.7590 -0.9789 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3559 0.4077 -0.8814 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5577 -0.3912 -0.0555 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9202 2.5450 -1.8092 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2733 -0.3615 1.3336 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3935 -0.9815 0.2557 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0492 -3.8593 -1.9470 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4172 -0.2217 -1.5515 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5005 1.3826 0.2977 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1557 1.5656 -1.4312 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2396 2.5402 -0.1826 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0992 -0.3912 0.3535 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5476 -0.0832 2.1096 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3881 1.3230 2.0590 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1668 1.6475 1.9203 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4476 2.5026 -1.1572 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8860 1.6607 -1.1978 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2906 2.6167 0.2431 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2721 -2.6121 -2.6815 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3157 -2.6711 2.2698 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9278 -2.4227 1.5218 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8629 -0.3865 2.6108 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4749 1.9159 1.1396 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8983 3.3526 -0.3361 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1649 -0.0564 -1.4401 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7713 -1.4621 0.0007 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9138 2.6044 -1.6551 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5781 -3.8224 -2.7518 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 3 5 1 0 3 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 14 22 1 0 22 23 1 0 9 24 1 0 7 25 1 0 25 2 1 0 23 6 1 0 23 10 2 0 20 15 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 0 4 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 5 35 1 0 8 36 1 0 13 37 1 0 13 38 1 0 14 39 1 0 16 40 1 0 17 41 1 0 19 42 1 0 20 43 1 0 21 44 1 0 24 45 1 0 M END

Standard InCHIKey	KITUBOBTRYFYBY-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H20O5/c1-10-20(2,3)18-16(24-10)9-14(23)17-13(22)8-15(25-19(17)18)11-4-6-12(21)7-5-11/h4-7,9-10,15,21,23H,8H2,1-3H3
SMILES	CC1C(C)(C)c2c(cc(c3C(=O)CC(c4ccc(cc4)O)Oc23)O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	340.13	Volume:	345.746 ? Van der Waals volume.
Dense:	0.984	LogP:	3.344 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.022 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.633 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	22.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.824	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.653	Fsp³:	0.35
MCE-18:	82.407 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.581	Fluc inhibitor:	0.289 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.476 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.357 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.297	Promiscuous compounds:	0.013

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.888	MDCK Permeability:	-4.749
Pgp-inhibitor:	0.979	Pgp-substrate:	0.18
PAMPA:	0.099 ? 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):	0.001
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.868
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.033	MRP1:	0.984
Plasma Protein Binding (PPB):	96.81%	Volume Distribution (VD):	0.191
Fu:	2.608% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.883
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.993
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.603	CYP1A2-substrate:	0.405
CYP2C19-inhibitor:	0.475	CYP2C19-substrate:	0.964
CYP2C9-inhibitor:	0.89	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.026	CYP2D6-substrate:	0.615
CYP3A4-inhibitor:	0.275	CYP3A4-substrate:	0.875
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.985
HLM stability:	0.79 ? 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):

3.712

Half-life (T1/2):

1.278

ADMET: Toxicity

hERG Blockers:	0.149	hERG Blockers (10um):	0.591
Human Hepatotoxicity (H-HT):	0.652	Drug-induced Liver Injury (DILI):	0.488
AMES Toxicity:	0.57	Rat Oral Acute Toxicity:	0.667
Maximum Recommended Daily Dose:	0.711	Skin Sensitization:	0.773
Carcinogencity:	0.66	Eye Corrosion:	0.003
Eye Irritation:	0.962	Respiratory Toxicity:	0.758
Drug-induced Neurotoxicity:	0.408	Ototoxicity:	0.457
Hematotoxicity:	0.236	Drug-induced Nephrotoxicity:	0.556
Genotoxicity:	0.745	RPMI-8226 Immunitoxicity:	0.098
A549 Cytotoxicity:	0.475	Hek293 Cytotoxicity:	0.796
BCF:	1.672 ? 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:	4.312 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.817 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.111 ? 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
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[19583252]
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[28169537]
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11959	Helminthostachys zeylanica	Species	Ophioglossaceae	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 NPC191660 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	22462
0.1-0.2	22954
0.2-0.3	3668
0.3-0.4	561
0.4-0.5	181
0.5-0.6	30
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	Natural Product ID
0.619	Remote Similarity	NPC220998
0.5965	Remote Similarity	NPC603284
0.5938	Remote Similarity	NPC470133
0.5763	Remote Similarity	NPC329203
0.5763	Remote Similarity	NPC324386
0.5763	Remote Similarity	NPC222342
0.569	Remote Similarity	NPC32441
0.569	Remote Similarity	NPC79943
0.55	Remote Similarity	NPC194432
0.5469	Remote Similarity	NPC480991
0.541	Remote Similarity	NPC485881
0.541	Remote Similarity	NPC469764
0.541	Remote Similarity	NPC606248
0.5385	Remote Similarity	NPC107572
0.5385	Remote Similarity	NPC32739
0.5373	Remote Similarity	NPC76338
0.5373	Remote Similarity	NPC250242
0.5333	Remote Similarity	NPC167624
0.5333	Remote Similarity	NPC166482
0.5303	Remote Similarity	NPC175504
0.5286	Remote Similarity	NPC69531
0.5278	Remote Similarity	NPC475052
0.5254	Remote Similarity	NPC225153
0.5254	Remote Similarity	NPC479876
0.5246	Remote Similarity	NPC300668
0.5205	Remote Similarity	NPC479210
0.5172	Remote Similarity	NPC329225
0.5172	Remote Similarity	NPC147686
0.5161	Remote Similarity	NPC475267
0.5152	Remote Similarity	NPC109183
0.5152	Remote Similarity	NPC472580

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC191660 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4159
0.1-0.2	4880
0.2-0.3	99
0.3-0.4	7
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
0.569	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5172	Remote Similarity	NPD1549	Phase 2

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