NPASS Compound

Natural Product: NPC177475

Natural Product ID	NPC177475
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Threo-Guaiacylglycerol
IUPAC Name	(1S,2S)-1-(4-hydroxy-3-methoxyphenyl)propane-1,2,3-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3608840
PubChem CID	12310249
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 29 29 0 0 0 0 0 0 0 0999 V2000 3.5971 -1.8491 -0.0400 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5460 -0.4834 -0.3319 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3469 0.2278 -0.2909 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1790 -0.4188 0.0437 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0460 0.2541 0.0974 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0222 1.5969 -0.2018 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1499 2.2652 -0.5419 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3352 1.5755 -0.5854 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5117 2.2499 -0.9275 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2740 -0.4618 0.4570 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4797 0.3782 0.1081 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7613 -0.3998 0.4033 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7819 -0.6389 1.7784 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4678 0.6109 -1.2583 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3277 -1.6727 -0.2309 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5608 -2.2645 -0.4548 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7709 -2.4395 -0.4780 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6216 -1.9905 1.0672 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1450 -1.4676 0.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9297 2.1860 -0.1820 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1388 3.3340 -0.7751 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3765 1.8152 -0.6626 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2668 -0.6744 1.5330 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5246 1.2867 0.7175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5991 0.2922 0.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7552 -1.3164 -0.1902 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6719 -0.4315 2.1722 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7341 0.1466 -1.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6374 -1.7103 -0.9628 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 5 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 11 14 1 0 10 15 1 0 8 3 1 0 1 16 1 0 1 17 1 0 1 18 1 0 4 19 1 0 6 20 1 0 7 21 1 0 9 22 1 0 10 23 1 1 11 24 1 1 12 25 1 0 12 26 1 0 13 27 1 0 14 28 1 0 15 29 1 0 M END

Standard InCHIKey	LSKFUSLVUZISST-WPRPVWTQSA-N
Standard InCHI	InChI=1S/C10H14O5/c1-15-9-4-6(2-3-7(9)12)10(14)8(13)5-11/h2-4,8,10-14H,5H2,1H3/t8-,10-/m0/s1
SMILES	COc1cc(ccc1O)[C@@H]([C@H](CO)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	214.08	Volume:	209.002 ? Van der Waals volume.
Dense:	1.024	LogP:	-0.162 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.125 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.105 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	6.0
TPSA:	90.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	4.0	Rings:	1.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.556	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.913	Fsp³:	0.4
MCE-18:	16.0 ? 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:	0.422	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? 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:	0.453	Promiscuous compounds:	0.708

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.031	MDCK Permeability:	-4.84
Pgp-inhibitor:	0.0	Pgp-substrate:	0.079
PAMPA:	0.905 ? 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):	0.069
20% Bioavailability (F20%):	0.259	30% Bioavailability (F30%):	0.427
50% Bioavailability (F50%):	0.88

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.112	MRP1:	0.131
Plasma Protein Binding (PPB):	39.971%	Volume Distribution (VD):	-0.156
Fu:	58.301% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.457
BSEP inhibitor:	0.005

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.007	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.163	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.02	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.246
HLM stability:	0.021 ? 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):

5.995

Half-life (T1/2):

1.781

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.113
Human Hepatotoxicity (H-HT):	0.411	Drug-induced Liver Injury (DILI):	0.009
AMES Toxicity:	0.566	Rat Oral Acute Toxicity:	0.039
Maximum Recommended Daily Dose:	0.041	Skin Sensitization:	0.873
Carcinogencity:	0.286	Eye Corrosion:	0.012
Eye Irritation:	0.872	Respiratory Toxicity:	0.027
Drug-induced Neurotoxicity:	0.06	Ototoxicity:	0.761
Hematotoxicity:	0.053	Drug-induced Nephrotoxicity:	0.162
Genotoxicity:	0.033	RPMI-8226 Immunitoxicity:	0.058
A549 Cytotoxicity:	0.061	Hek293 Cytotoxicity:	0.075
BCF:	0.39 ? 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:	2.283 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.634 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.873 ? 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
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	skin-removed stems	Pingle Town, Sichuang Province, China	2008-AUG	PMID[21469695]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	stem	n.a.	PMID[21469695]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22690646]
NPO28765	Miliusa balansae	Species	Annonaceae	Eukaryota	leaves	n.a.	n.a.	PMID[26238320]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	bark	n.a.	PMID[26767291]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26767291]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28765	Miliusa balansae	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28765	Miliusa balansae	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16850	Eucommia ulmoides	Species	Eucommiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO28765	Miliusa balansae	Species	Annonaceae	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
Inhibition	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	Inhibition	=	48.4	%	PMID[26238320]

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 NPC177475 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	21918
0.1-0.2	22309
0.2-0.3	4845
0.3-0.4	591
0.4-0.5	152
0.5-0.6	21
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC35071
1.0	High Similarity	NPC148615
0.7778	Intermediate Similarity	NPC181969
0.7027	Intermediate Similarity	NPC320987
0.6875	Remote Similarity	NPC601893
0.6757	Remote Similarity	NPC165375
0.6757	Remote Similarity	NPC220598
0.65	Remote Similarity	NPC476343
0.641	Remote Similarity	NPC326599
0.641	Remote Similarity	NPC329595
0.6047	Remote Similarity	NPC165045
0.6047	Remote Similarity	NPC118533
0.5854	Remote Similarity	NPC255675
0.5814	Remote Similarity	NPC195292
0.575	Remote Similarity	NPC135961
0.5581	Remote Similarity	NPC325625
0.5577	Remote Similarity	NPC65942
0.5577	Remote Similarity	NPC248307
0.551	Remote Similarity	NPC310854
0.549	Remote Similarity	NPC480703
0.5405	Remote Similarity	NPC7097
0.5366	Remote Similarity	NPC221049
0.5306	Remote Similarity	NPC470990
0.5294	Remote Similarity	NPC92164
0.525	Remote Similarity	NPC604189
0.5238	Remote Similarity	NPC139519
0.5238	Remote Similarity	NPC471693
0.5217	Remote Similarity	NPC476968
0.5192	Remote Similarity	NPC9370
0.5192	Remote Similarity	NPC287495
0.5111	Remote Similarity	NPC209567
0.5094	Remote Similarity	NPC174495
0.5091	Remote Similarity	NPC75695

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC177475 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4207
0.1-0.2	4658
0.2-0.3	266
0.3-0.4	16
0.4-0.5	3
0.5-0.6	0
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
		NPD

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