NPASS Compound

Natural Product: NPC476343

Natural Product ID	NPC476343
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Guaicylglycerol
IUPAC Name	1-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)propane-1,3-diol
Synonyms	Guaicylglycerol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL573104
PubChem CID	45482328
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 32 32 0 0 0 0 0 0 0 0999 V2000 -2.8187 2.2368 0.7798 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1009 1.0551 1.0164 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8813 0.3897 -0.3133 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1214 -0.8947 -0.2163 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2311 -0.7230 0.3712 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4939 -1.1103 1.6700 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7404 -0.9648 2.2458 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7880 -0.4191 1.5369 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5444 -0.0267 0.2389 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2813 -0.1771 -0.3361 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6125 0.5214 -0.4606 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3786 0.9313 -1.8004 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0532 -0.2724 2.1238 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0425 -1.4278 -1.5159 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 0.0527 -0.8713 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8858 -0.8139 0.0528 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5576 2.6680 -0.0748 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1518 1.2512 1.5507 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7643 0.4056 1.6272 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4297 1.0941 -1.0516 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7305 -1.6199 0.3606 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3220 -1.5382 2.2302 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9316 -1.2724 3.2634 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1192 0.1408 -1.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6708 1.8040 -1.7521 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9549 0.1240 -2.4233 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3376 1.3216 -2.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8817 -0.6836 1.6847 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1483 -0.7317 -2.1840 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1950 -0.5251 -1.8135 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8944 0.9459 -0.9487 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7135 -1.7413 -0.1739 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 4 14 1 0 3 15 1 0 15 16 1 0 10 5 1 0 1 17 1 0 2 18 1 0 2 19 1 0 3 20 1 0 4 21 1 0 6 22 1 0 7 23 1 0 10 24 1 0 12 25 1 0 12 26 1 0 12 27 1 0 13 28 1 0 14 29 1 0 15 30 1 0 15 31 1 0 16 32 1 0 M END

Standard InCHIKey	SKRUGJGVXQATKU-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C11H16O5/c1-16-10-4-7(2-3-9(10)14)11(15)8(5-12)6-13/h2-4,8,11-15H,5-6H2,1H3
SMILES	OCC(C(c1ccc(c(c1)OC)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	228.1	Volume:	226.298 ? Van der Waals volume.
Dense:	1.008	LogP:	-0.447 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.071 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.41 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	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:	0.571	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.849	Fsp³:	0.455
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:	0.099	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.103 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.392	Promiscuous compounds:	0.552

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.973	MDCK Permeability:	-4.653
Pgp-inhibitor:	0.0	Pgp-substrate:	0.066
PAMPA:	0.987 ? 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):	0.98
20% Bioavailability (F20%):	0.754	30% Bioavailability (F30%):	0.931
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.01	MRP1:	0.742
Plasma Protein Binding (PPB):	41.228%	Volume Distribution (VD):	0.22
Fu:	52.676% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.024
OATP1B3 inhibitor:	0.662	BCRP inhibitor:	0.176
BSEP inhibitor:	0.006

ADMET: Metabolism

CYP1A2-inhibitor:	0.036	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.074	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.614	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.04	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.004
HLM stability:	0.011 ? 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):

7.697

Half-life (T1/2):

2.083

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.298
Human Hepatotoxicity (H-HT):	0.456	Drug-induced Liver Injury (DILI):	0.034
AMES Toxicity:	0.232	Rat Oral Acute Toxicity:	0.026
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.483
Carcinogencity:	0.382	Eye Corrosion:	0.005
Eye Irritation:	0.675	Respiratory Toxicity:	0.057
Drug-induced Neurotoxicity:	0.162	Ototoxicity:	0.92
Hematotoxicity:	0.104	Drug-induced Nephrotoxicity:	0.379
Genotoxicity:	0.008	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.034	Hek293 Cytotoxicity:	0.13
BCF:	0.223 ? 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:	2.091 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.665 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.829 ? 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
NPO12339	Daphne feddei	Species	Thymelaeaceae	Eukaryota	stem bark	Kunming, Yunnan Province, China	n.a.	PMID[18986199]
NPO12339	Daphne feddei	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12339	Daphne feddei	Species	Thymelaeaceae	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
IC50	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	IC50	>	300000.0	nM	PMID[7783154]

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 NPC476343 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	23196
0.1-0.2	21765
0.2-0.3	4174
0.3-0.4	526
0.4-0.5	153
0.5-0.6	25
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7027	Intermediate Similarity	NPC320987
0.7	Intermediate Similarity	NPC195292
0.6829	Remote Similarity	NPC165045
0.6829	Remote Similarity	NPC118533
0.65	Remote Similarity	NPC35071
0.65	Remote Similarity	NPC177475
0.65	Remote Similarity	NPC148615
0.641	Remote Similarity	NPC326599
0.641	Remote Similarity	NPC181969
0.641	Remote Similarity	NPC329595
0.5957	Remote Similarity	NPC470990
0.5882	Remote Similarity	NPC272
0.5882	Remote Similarity	NPC77040
0.5882	Remote Similarity	NPC485398
0.5714	Remote Similarity	NPC85488
0.549	Remote Similarity	NPC475875
0.5455	Remote Similarity	NPC480479
0.5455	Remote Similarity	NPC280704
0.5405	Remote Similarity	NPC7097
0.5366	Remote Similarity	NPC160380
0.5366	Remote Similarity	NPC38996
0.5366	Remote Similarity	NPC221049
0.5333	Remote Similarity	NPC242807
0.5333	Remote Similarity	NPC153739
0.525	Remote Similarity	NPC309203
0.525	Remote Similarity	NPC604189
0.5238	Remote Similarity	NPC139519
0.5217	Remote Similarity	NPC487676
0.5217	Remote Similarity	NPC476968
0.52	Remote Similarity	NPC310854
0.5116	Remote Similarity	NPC255675
0.5091	Remote Similarity	NPC100675
0.5091	Remote Similarity	NPC101624
0.5091	Remote Similarity	NPC184938
0.5091	Remote Similarity	NPC601691

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476343 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4127
0.1-0.2	4737
0.2-0.3	268
0.3-0.4	15
0.4-0.5	2
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