NPASS Compound

Natural Product: NPC222876

Natural Product ID	NPC222876
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Merulinic Acid C
IUPAC Name	2-[(Z)-heptadec-8-enyl]-6-hydroxybenzoic acid
Synonyms	Merulinic Acid C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479333
PubChem CID	10384819
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0001248] Hydroxybenzoic acid derivatives [CHEMONTID:0000487] Salicylic acid and derivatives [CHEMONTID:0002514] Salicylic acids

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 65 65 0 0 0 0 0 0 0 0999 V2000 4.8666 2.8408 1.3251 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3049 2.5736 1.0221 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4770 1.3094 0.2631 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9716 0.1280 1.0287 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1981 -1.1430 0.3253 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6824 -1.4023 -0.9934 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3288 -1.5210 -1.4384 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2442 -0.5551 -1.4711 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6778 0.0417 -0.2798 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4209 -0.1578 0.0696 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4820 -0.9776 -0.6764 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0482 -2.1378 0.1836 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0163 -2.9880 -0.5709 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2294 -2.2324 -1.0500 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9275 -1.6740 0.1435 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1779 -0.8860 -0.2039 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7420 -0.4032 1.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9638 0.3695 0.8704 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1666 -0.2856 1.0265 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3582 0.3392 0.8175 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3112 1.6653 0.4399 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1411 2.3400 0.2776 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9319 1.6787 0.4978 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6970 2.4356 0.3285 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2237 3.0347 1.3526 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9823 2.5774 -0.8269 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1019 3.6832 -0.1050 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4232 2.0715 1.9701 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2845 2.8860 0.3623 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7749 3.8253 1.8407 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7323 3.4063 0.3946 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9180 2.5171 1.9600 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5849 1.1320 0.1184 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9966 1.4093 -0.7368 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6879 0.1079 1.9589 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0014 0.1942 1.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8197 -1.9752 1.0445 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3314 -1.3516 0.3952 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2167 -2.3916 -1.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2377 -0.6878 -1.7581 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8903 -2.4528 -0.8548 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3292 -1.9909 -2.5299 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7223 0.3814 -2.0177 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4628 -0.7949 -2.2574 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2812 0.7229 0.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0550 0.3271 0.9856 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4035 -0.2978 -0.9115 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7736 -1.3816 -1.6342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4408 -1.7895 1.1430 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8449 -2.7580 0.4031 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4925 -3.5034 -1.4016 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3765 -3.7757 0.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9921 -1.4805 -1.8208 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8923 -2.9836 -1.5503 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2462 -2.5152 0.7858 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2701 -0.9858 0.6976 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9053 -1.5033 -0.7720 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8687 -0.0617 -0.8423 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9480 0.1907 1.6145 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9545 -1.3080 1.7373 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1879 -1.3441 1.3283 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2795 -0.2153 0.9522 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2387 2.1949 0.2645 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5573 3.4699 -1.1144 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9498 4.0581 -0.5135 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 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 22 27 1 0 23 18 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 0 2 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 6 39 1 0 6 40 1 0 7 41 1 0 7 42 1 0 8 43 1 0 8 44 1 0 9 45 1 0 10 46 1 0 11 47 1 0 11 48 1 0 12 49 1 0 12 50 1 0 13 51 1 0 13 52 1 0 14 53 1 0 14 54 1 0 15 55 1 0 15 56 1 0 16 57 1 0 16 58 1 0 17 59 1 0 17 60 1 0 19 61 1 0 20 62 1 0 21 63 1 0 26 64 1 0 27 65 1 0 M END

Standard InCHIKey	NRSDQEWAMHRTMK-KTKRTIGZSA-N
Standard InCHI	InChI=1S/C24H38O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-18-21-19-17-20-22(25)23(21)24(26)27/h9-10,17,19-20,25H,2-8,11-16,18H2,1H3,(H,26,27)/b10-9-
SMILES	CCCCCCCC/C=CCCCCCCCc1cccc(c1C(=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.28	Volume:	428.292 ? Van der Waals volume.
Dense:	0.874	LogP:	8.182 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.122 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.645 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	8.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.236	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.327	Fsp³:	0.625
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:	1	PAINS Alert:	0
Colloidal aggregators:	0.634	Fluc inhibitor:	0.31 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.035 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.266 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.8	Promiscuous compounds:	0.287

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.084	MDCK Permeability:	-4.702
Pgp-inhibitor:	0.916	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):	0.034
20% Bioavailability (F20%):	0.329	30% Bioavailability (F30%):	0.938
50% Bioavailability (F50%):	0.723

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.987
Plasma Protein Binding (PPB):	98.74%	Volume Distribution (VD):	-0.489
Fu:	0.255% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.133
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.738
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.022
CYP2D6-inhibitor:	0.95	CYP2D6-substrate:	0.406
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.047 ? 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):

2.252

Half-life (T1/2):

1.129

ADMET: Toxicity

hERG Blockers:	0.27	hERG Blockers (10um):	0.455
Human Hepatotoxicity (H-HT):	0.329	Drug-induced Liver Injury (DILI):	0.038
AMES Toxicity:	0.105	Rat Oral Acute Toxicity:	0.118
Maximum Recommended Daily Dose:	0.146	Skin Sensitization:	1.0
Carcinogencity:	0.039	Eye Corrosion:	0.975
Eye Irritation:	0.995	Respiratory Toxicity:	0.932
Drug-induced Neurotoxicity:	0.006	Ototoxicity:	0.275
Hematotoxicity:	0.038	Drug-induced Nephrotoxicity:	0.694
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.808	Hek293 Cytotoxicity:	0.236
BCF:	0.822 ? 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:	4.526 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.04 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.388 ? 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
NPO22584	Thelephora vialis	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16901696]
NPO22584	Thelephora vialis	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16152	Phlebia radiata	Species	Meruliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22584	Thelephora vialis	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22584	Thelephora vialis	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16152	Phlebia radiata	Species	Meruliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO32809	merulius tremellosus	Species	Meruliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO16152	Phlebia radiata	Species	Meruliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22584	Thelephora vialis	Species	Thelephoraceae	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
MIC	5

Activity Type	# Activity
Organism	5

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
NPT1388	Organism	Arthrobacter citreus	Arthrobacter citreus	MIC	=	0.4	ug.mL-1	PMID[14987072]
NPT1390	Organism	Kocuria rosea	Kocuria rosea	MIC	=	0.4	ug.mL-1	PMID[14987072]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	0.4	ug.mL-1	PMID[14987072]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	0.4	ug.mL-1	PMID[14987072]
NPT1389	Organism	Clavibacter michiganensis subsp. insidiosus	Clavibacter michiganensis subsp. insidiosus	MIC	=	0.4	ug.mL-1	PMID[14987072]

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 NPC222876 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	19493
0.1-0.2	27708
0.2-0.3	2373
0.3-0.4	209
0.4-0.5	45
0.5-0.6	4
0.6-0.7	2
0.7-0.8	0
0.8-0.85	4
0.85-0.9	8
0.9-0.95	1
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC244994
1.0	High Similarity	NPC292665
1.0	High Similarity	NPC179092
0.9778	High Similarity	NPC238531
0.9778	High Similarity	NPC178395
0.9556	High Similarity	NPC483452
0.9375	High Similarity	NPC301987
0.898	High Similarity	NPC115188
0.898	High Similarity	NPC159760
0.8667	High Similarity	NPC483451
0.8667	High Similarity	NPC227450
0.8667	High Similarity	NPC272454
0.8667	High Similarity	NPC35856
0.8667	High Similarity	NPC609957
0.86	High Similarity	NPC26433
0.8431	Intermediate Similarity	NPC167055
0.8235	Intermediate Similarity	NPC184579
0.8235	Intermediate Similarity	NPC233165
0.8148	Intermediate Similarity	NPC240744
0.7255	Intermediate Similarity	NPC605990
0.7059	Intermediate Similarity	NPC244351
0.7059	Intermediate Similarity	NPC483453
0.6981	Remote Similarity	NPC17840
0.6981	Remote Similarity	NPC247477
0.5593	Remote Similarity	NPC489602
0.5373	Remote Similarity	NPC71256
0.5185	Remote Similarity	NPC607458
0.5167	Remote Similarity	NPC486906

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC222876 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3203
0.1-0.2	5569
0.2-0.3	363
0.3-0.4	15
0.4-0.5	0
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