NPASS Compound

Natural Product: NPC255675

Natural Product ID	NPC255675
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QGFJORGLNPWXMK-MRVPVSSYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3326612
PubChem CID	NA
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0000190] Methoxyphenols

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 28 28 0 0 0 0 0 0 0 0999 V2000 -3.1164 1.1128 -1.8519 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6046 -0.0717 -1.3869 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3970 -0.1020 0.0977 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3905 0.8908 0.5925 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0498 0.6936 0.0132 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3090 1.3388 -1.1665 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5645 1.1366 -1.6849 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4291 0.3072 -1.0292 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0921 -0.3510 0.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8290 -0.1391 0.6646 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9972 -1.1856 0.7926 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5958 -1.8229 1.9886 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7093 0.0939 -1.5473 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6149 0.1048 0.7174 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7800 1.8989 -1.3572 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2699 -0.9116 -1.6697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6424 -0.2667 -1.9390 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0550 -1.1231 0.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3058 0.7701 1.6911 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6893 1.9405 0.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3996 1.9800 -1.6472 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8341 1.6412 -2.6004 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5252 -0.6395 1.5961 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4824 -1.1078 2.8360 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4069 -2.5611 2.2340 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6467 -2.3796 1.8350 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2101 -0.7362 -1.3089 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3160 -0.5113 0.4465 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 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 1 0 8 13 1 0 3 14 1 0 10 5 1 0 1 15 1 0 2 16 1 0 2 17 1 0 3 18 1 1 4 19 1 0 4 20 1 0 6 21 1 0 7 22 1 0 10 23 1 0 12 24 1 0 12 25 1 0 12 26 1 0 13 27 1 0 14 28 1 0 M END

Standard InCHIKey	QGFJORGLNPWXMK-MRVPVSSYSA-N
Standard InCHI	InChI=1S/C10H14O4/c1-14-10-5-7(2-3-9(10)13)4-8(12)6-11/h2-3,5,8,11-13H,4,6H2,1H3/t8-/m1/s1
SMILES	OC[C@@H](Cc1ccc(c(c1)OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	198.09	Volume:	200.211 ? Van der Waals volume.
Dense:	0.989	LogP:	0.177 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.456 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.44 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	6.0
TPSA:	69.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.65	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.403	Fsp³:	0.4
MCE-18:	14.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.351	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.016 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.713	Promiscuous compounds:	0.506

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.495	MDCK Permeability:	-4.874
Pgp-inhibitor:	0.0	Pgp-substrate:	0.785
PAMPA:	0.873 ? 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%):	0.164	30% Bioavailability (F30%):	0.197
50% Bioavailability (F50%):	0.753

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.246
Plasma Protein Binding (PPB):	35.867%	Volume Distribution (VD):	-0.238
Fu:	61.803% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.147
BSEP inhibitor:	0.4

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.015	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.93	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.992	CYP2D6-substrate:	0.076
CYP3A4-inhibitor:	0.038	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.009
HLM stability:	0.726 ? 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):

9.428

Half-life (T1/2):

1.739

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.233
Human Hepatotoxicity (H-HT):	0.285	Drug-induced Liver Injury (DILI):	0.009
AMES Toxicity:	0.566	Rat Oral Acute Toxicity:	0.029
Maximum Recommended Daily Dose:	0.058	Skin Sensitization:	0.906
Carcinogencity:	0.361	Eye Corrosion:	0.444
Eye Irritation:	0.978	Respiratory Toxicity:	0.029
Drug-induced Neurotoxicity:	0.041	Ototoxicity:	0.744
Hematotoxicity:	0.087	Drug-induced Nephrotoxicity:	0.323
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.016	Hek293 Cytotoxicity:	0.087
BCF:	0.26 ? 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:	2.311 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.707 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.976 ? 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
NPO15339	Artemisia afra	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[23506561]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	leaves	n.a.	n.a.	PMID[25127165]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8843	Epipactis palustris	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15339	Artemisia afra	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15050	Rumex obtusifolius	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15050	Rumex obtusifolius	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15050	Rumex obtusifolius	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8843	Epipactis palustris	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15050	Rumex obtusifolius	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2373	Popillia japonica	Species	Scarabaeidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15339	Artemisia afra	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

Activity Type	# Activity
Activity	2

Activity Type	# Activity
Others	2

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
NPT35	Others	n.a.	n.a.	Activity	=	3.59	uM	PMID[25127165]
NPT35	Others	n.a.	n.a.	Activity	=	28.2	uM	PMID[25127165]

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 NPC255675 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	22528
0.1-0.2	20235
0.2-0.3	6011
0.3-0.4	737
0.4-0.5	258
0.5-0.6	58
0.6-0.7	16
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC471693
0.7222	Intermediate Similarity	NPC221049
0.6944	Remote Similarity	NPC257124
0.6857	Remote Similarity	NPC156840
0.6667	Remote Similarity	NPC85488
0.6316	Remote Similarity	NPC8547
0.6316	Remote Similarity	NPC140359
0.619	Remote Similarity	NPC312675
0.619	Remote Similarity	NPC262156
0.619	Remote Similarity	NPC184651
0.619	Remote Similarity	NPC113865
0.6154	Remote Similarity	NPC165133
0.6154	Remote Similarity	NPC242885
0.6154	Remote Similarity	NPC95614
0.6154	Remote Similarity	NPC193544
0.6154	Remote Similarity	NPC232316
0.6098	Remote Similarity	NPC197757
0.6047	Remote Similarity	NPC487676
0.5854	Remote Similarity	NPC35071
0.5854	Remote Similarity	NPC177475
0.5854	Remote Similarity	NPC57490
0.5854	Remote Similarity	NPC148615
0.5854	Remote Similarity	NPC603326
0.5854	Remote Similarity	NPC603989
0.5814	Remote Similarity	NPC203133
0.5745	Remote Similarity	NPC343720
0.5745	Remote Similarity	NPC54872
0.5714	Remote Similarity	NPC17943
0.5714	Remote Similarity	NPC299406
0.5714	Remote Similarity	NPC325625
0.5682	Remote Similarity	NPC117214
0.5682	Remote Similarity	NPC56214
0.5682	Remote Similarity	NPC476968
0.5652	Remote Similarity	NPC473853
0.5652	Remote Similarity	NPC98631
0.5652	Remote Similarity	NPC5428
0.5652	Remote Similarity	NPC206615
0.5652	Remote Similarity	NPC470212
0.5652	Remote Similarity	NPC481914
0.5652	Remote Similarity	NPC607444
0.5556	Remote Similarity	NPC7097
0.5532	Remote Similarity	NPC324571
0.5526	Remote Similarity	NPC293619
0.55	Remote Similarity	NPC320987
0.5455	Remote Similarity	NPC194416
0.5455	Remote Similarity	NPC31344
0.5455	Remote Similarity	NPC177291
0.5455	Remote Similarity	NPC317769
0.5455	Remote Similarity	NPC127937
0.5435	Remote Similarity	NPC78974
0.5435	Remote Similarity	NPC127587
0.5417	Remote Similarity	NPC164386
0.5385	Remote Similarity	NPC604189
0.5366	Remote Similarity	NPC139519
0.5366	Remote Similarity	NPC181969
0.5333	Remote Similarity	NPC66518
0.5306	Remote Similarity	NPC137427
0.5294	Remote Similarity	NPC310718
0.5217	Remote Similarity	NPC51840
0.5217	Remote Similarity	NPC227217
0.5217	Remote Similarity	NPC117780
0.5217	Remote Similarity	NPC82679
0.5208	Remote Similarity	NPC311680
0.5208	Remote Similarity	NPC212015
0.5208	Remote Similarity	NPC103823
0.52	Remote Similarity	NPC311595
0.52	Remote Similarity	NPC481913
0.52	Remote Similarity	NPC24474
0.5128	Remote Similarity	NPC246358
0.5128	Remote Similarity	NPC203719
0.5116	Remote Similarity	NPC78918
0.5116	Remote Similarity	NPC476343
0.5116	Remote Similarity	NPC139617
0.5106	Remote Similarity	NPC470804
0.5102	Remote Similarity	NPC472090
0.5102	Remote Similarity	NPC303680

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC255675 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3996
0.1-0.2	4756
0.2-0.3	373
0.3-0.4	21
0.4-0.5	3
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
0.6944	Remote Similarity	NPD228	Phase 0

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