NPASS Compound

Natural Product: NPC488412

Natural Product ID	NPC488412
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AQQHSHZEHBOYKP-FPLPWBNLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101792029
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0001286] Benzenediols [CHEMONTID:0000137] Resorcinols

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 51 51 0 0 0 0 0 0 0 0999 V2000 5.7349 -0.1723 -2.2216 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3394 -0.4218 -0.8539 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4083 -1.2090 0.0397 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1086 -0.5211 0.2756 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2775 0.8307 0.9379 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9058 1.4891 1.1544 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1063 0.6372 2.0006 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9664 0.1242 1.6252 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4091 0.3744 0.3098 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9605 1.0683 0.4034 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8981 0.2049 1.1614 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1808 -1.1391 0.6151 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8099 -1.2072 -0.7313 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1337 -0.5468 -0.7209 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3354 0.7753 -1.0275 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6278 1.3012 -0.9811 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6977 0.5044 -0.6311 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5149 -0.8259 -0.3199 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2377 -1.3210 -0.3719 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6129 -1.6176 0.0327 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3306 1.1756 -0.5741 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -5.8575 2.6282 -1.2849 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8005 -0.7271 -2.3188 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5012 0.9153 -2.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4468 -0.4278 -3.0398 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2918 -0.9639 -1.0195 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6024 0.5631 -0.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2490 -2.1878 -0.4439 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9440 -1.3916 0.9867 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5652 -0.4456 -0.6906 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4913 -1.1720 0.9277 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7712 0.6527 1.9153 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8921 1.4477 0.2472 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5630 1.8224 0.2039 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1335 2.4273 1.7560 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5278 0.4381 3.0163 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4245 -0.5217 2.3501 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1250 -0.6528 -0.0937 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0278 0.7939 -0.4645 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7965 1.9930 1.0092 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2737 1.4046 -0.5839 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8914 0.7244 1.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5084 0.0899 2.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9245 -1.6159 1.3301 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3285 -1.8500 0.6281 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1550 -0.8203 -1.5397 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9624 -2.2851 -0.9713 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5136 1.4022 -1.3042 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1125 -2.3731 -0.1231 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5219 -2.6246 0.0720 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4272 3.2530 -0.7483 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 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 17 21 1 0 16 22 1 0 19 14 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 3 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 6 34 1 0 6 35 1 0 7 36 1 0 8 37 1 0 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 11 42 1 0 11 43 1 0 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 15 48 1 0 19 49 1 0 20 50 1 0 22 51 1 0 M END

Standard InCHIKey	AQQHSHZEHBOYKP-FPLPWBNLSA-N
Standard InCHI	InChI=1S/C19H29ClO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-14-17(21)19(20)18(22)15-16/h7-8,14-15,21-22H,2-6,9-13H2,1H3/b8-7-
SMILES	CCCCCC/C=CCCCCCc1cc(c(c(c1)O)Cl)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	324.19	Volume:	350.869 ? Van der Waals volume.
Dense:	0.924	LogP:	7.466 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.368 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.561 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	7.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.366	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.417	Fsp³:	0.579
MCE-18:	7.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.862	Fluc inhibitor:	0.317 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.257 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.908	Promiscuous compounds:	0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.994	MDCK Permeability:	-4.696
Pgp-inhibitor:	0.216	Pgp-substrate:	0.0
PAMPA:	0.001 ? 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):	0.002
20% Bioavailability (F20%):	0.395	30% Bioavailability (F30%):	0.828
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.069	MRP1:	0.818
Plasma Protein Binding (PPB):	98.952%	Volume Distribution (VD):	0.203
Fu:	0.419% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.375
OATP1B3 inhibitor:	0.98	BCRP inhibitor:	0.515
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.96
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.04
CYP2D6-inhibitor:	0.114	CYP2D6-substrate:	0.74
CYP3A4-inhibitor:	0.036	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.907 ? 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):

5.45

Half-life (T1/2):

0.448

ADMET: Toxicity

hERG Blockers:	0.626	hERG Blockers (10um):	0.895
Human Hepatotoxicity (H-HT):	0.274	Drug-induced Liver Injury (DILI):	0.033
AMES Toxicity:	0.101	Rat Oral Acute Toxicity:	0.279
Maximum Recommended Daily Dose:	0.522	Skin Sensitization:	1.0
Carcinogencity:	0.08	Eye Corrosion:	0.996
Eye Irritation:	0.995	Respiratory Toxicity:	0.94
Drug-induced Neurotoxicity:	0.029	Ototoxicity:	0.251
Hematotoxicity:	0.019	Drug-induced Nephrotoxicity:	0.317
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.967	Hek293 Cytotoxicity:	0.753
BCF:	1.5 ? 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:	4.788 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.89 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.825 ? 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
NPO41023	Dictyostelium monochasioides	Species	n.a.	Eukaryota	Fruiting Bodies	n.a.	n.a.	PMID[28921976]
NPO41023	Dictyostelium monochasioides	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
NPT15	Cell line	Jurkat	Homo sapiens	Inhibition	<	50.0	%	PMID[28921976]

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 NPC488412 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	26181
0.1-0.2	21743
0.2-0.3	1680
0.3-0.4	149
0.4-0.5	50
0.5-0.6	24
0.6-0.7	16
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488413
0.8684	High Similarity	NPC488416
0.8286	Intermediate Similarity	NPC488411
0.8286	Intermediate Similarity	NPC488410
0.8286	Intermediate Similarity	NPC488409
0.7073	Intermediate Similarity	NPC488415
0.7073	Intermediate Similarity	NPC488414
0.7	Intermediate Similarity	NPC146798
0.7	Intermediate Similarity	NPC222522
0.7	Intermediate Similarity	NPC106396
0.7	Intermediate Similarity	NPC94351
0.7	Intermediate Similarity	NPC168303
0.6829	Remote Similarity	NPC232523
0.675	Remote Similarity	NPC53051
0.675	Remote Similarity	NPC24404
0.675	Remote Similarity	NPC313030
0.6512	Remote Similarity	NPC71002
0.6512	Remote Similarity	NPC249828
0.625	Remote Similarity	NPC470700
0.625	Remote Similarity	NPC54844
0.625	Remote Similarity	NPC39097
0.625	Remote Similarity	NPC302681
0.625	Remote Similarity	NPC118286
0.625	Remote Similarity	NPC109691
0.6136	Remote Similarity	NPC94139
0.6136	Remote Similarity	NPC302219
0.6136	Remote Similarity	NPC147284
0.6	Remote Similarity	NPC158253
0.5952	Remote Similarity	NPC39664
0.5909	Remote Similarity	NPC483454
0.5909	Remote Similarity	NPC162314
0.5778	Remote Similarity	NPC242342
0.5778	Remote Similarity	NPC85479
0.5682	Remote Similarity	NPC196479
0.56	Remote Similarity	NPC305603
0.5556	Remote Similarity	NPC166761
0.55	Remote Similarity	NPC294186
0.55	Remote Similarity	NPC147310
0.55	Remote Similarity	NPC137415
0.55	Remote Similarity	NPC166313
0.55	Remote Similarity	NPC192032
0.55	Remote Similarity	NPC24407
0.55	Remote Similarity	NPC11280
0.5455	Remote Similarity	NPC55561
0.5435	Remote Similarity	NPC10588
0.5435	Remote Similarity	NPC129373
0.5417	Remote Similarity	NPC210497
0.5366	Remote Similarity	NPC59506
0.5319	Remote Similarity	NPC204901
0.5319	Remote Similarity	NPC72947
0.5227	Remote Similarity	NPC177420
0.5106	Remote Similarity	NPC284011

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488412 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4256
0.1-0.2	4729
0.2-0.3	151
0.3-0.4	13
0.4-0.5	1
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