NPASS Compound

Natural Product: NPC476006

Natural Product ID	NPC476006
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Methyl-2-(4,8,12-Trimethyltrideca-3,7,11-Trienyl)-2H-Chromene-5,6-Diol
IUPAC Name	2-methyl-2-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl]chromene-5,6-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL521128
PubChem CID	14487959
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 66 0 0 0 0 0 0 0 0999 V2000 -0.2789 -3.2785 1.1394 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0900 -1.8914 0.6971 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1306 -1.0876 0.6472 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4390 -1.6064 1.0347 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5122 -1.6272 0.0280 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9521 -0.3403 -0.5735 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9169 0.4342 -1.3156 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0184 -0.7180 -1.5780 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2473 -0.2840 -1.5248 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6728 0.6073 -0.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7645 0.9905 0.4663 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4793 0.5400 0.4143 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0965 1.8419 1.5033 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3669 2.3307 1.6152 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3019 1.9428 0.6563 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9577 1.0959 -0.3691 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8867 0.7053 -1.3290 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.6122 2.4311 0.7495 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3280 -1.4523 0.3112 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3413 -0.0539 -0.1070 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5565 0.6503 -0.4833 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8289 0.3135 -0.4450 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8879 1.2730 -0.9135 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8562 1.7516 0.0771 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6579 0.7000 0.7159 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9774 0.6048 0.5022 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6401 1.5809 -0.3968 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7941 -0.4493 1.1381 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2113 -1.0421 0.0207 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6818 -3.8685 1.0772 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9588 -3.7839 0.4169 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6129 -3.3795 2.1898 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0005 -0.0678 0.3328 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3766 -2.6563 1.4577 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8390 -1.0271 1.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4241 -2.0553 0.5452 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2812 -2.4068 -0.7469 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1165 -0.1740 -1.7573 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5750 1.3205 -0.7426 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4267 0.9002 -2.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6606 -1.3919 -2.3565 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9499 -0.5969 -2.2761 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3526 2.1271 2.2340 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6405 2.9969 2.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7093 0.1539 -1.0895 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1437 2.5212 -0.1071 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9823 -1.6717 1.1618 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5219 -2.1436 -0.5663 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8523 0.6274 0.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5527 0.0361 -0.9365 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4250 1.7118 -0.9005 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3893 0.7318 -1.7792 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4215 2.1572 -1.4042 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3501 2.3587 0.8920 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5872 2.4728 -0.3812 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2598 -0.0276 1.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1560 1.6480 -1.3891 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7061 2.5903 0.0887 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7020 1.2808 -0.6090 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2600 -0.8349 2.0512 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9015 -1.2784 0.4071 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7723 -0.0536 1.4806 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3099 -1.2213 -0.2582 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2103 -1.0897 1.1179 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6707 -1.8687 -0.4804 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 15 18 1 0 2 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 3 26 27 1 0 26 28 1 0 22 29 1 0 12 6 1 0 16 10 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 7 38 1 0 7 39 1 0 7 40 1 0 8 41 1 0 9 42 1 0 13 43 1 0 14 44 1 0 17 45 1 0 18 46 1 0 19 47 1 0 19 48 1 0 20 49 1 0 20 50 1 0 21 51 1 0 23 52 1 0 23 53 1 0 24 54 1 0 24 55 1 0 25 56 1 0 27 57 1 0 27 58 1 0 27 59 1 0 28 60 1 0 28 61 1 0 28 62 1 0 29 63 1 0 29 64 1 0 29 65 1 0 M END

Standard InCHIKey	HDKOYWYEMWGKBR-VZLKJUJQSA-N
Standard InCHI	InChI=1S/C26H36O3/c1-19(2)9-6-10-20(3)11-7-12-21(4)13-8-17-26(5)18-16-22-24(29-26)15-14-23(27)25(22)28/h9,11,13-16,18,27-28H,6-8,10,12,17H2,1-5H3/b20-11+,21-13+
SMILES	C/C(=CCCC1(C)C=Cc2c(O1)ccc(c2O)O)/CC/C=C(/CCC=C(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	396.27	Volume:	449.055 ? Van der Waals volume.
Dense:	0.882	LogP:	7.49 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.54 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.059 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	14.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.336	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.698	Fsp³:	0.462
MCE-18:	48.842 ? 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:	1
Colloidal aggregators:	0.987	Fluc inhibitor:	0.046 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.341 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.397 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.668	Promiscuous compounds:	0.322

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.809	MDCK Permeability:	-4.712
Pgp-inhibitor:	0.995	Pgp-substrate:	0.0
PAMPA:	0.004 ? 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):	0.012
20% Bioavailability (F20%):	0.113	30% Bioavailability (F30%):	0.103
50% Bioavailability (F50%):	0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.984
Plasma Protein Binding (PPB):	97.162%	Volume Distribution (VD):	0.007
Fu:	2.612% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.0
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.421
CYP2C19-inhibitor:	0.992	CYP2C19-substrate:	0.034
CYP2C9-inhibitor:	0.977	CYP2C9-substrate:	0.045
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.716
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.503
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.442
HLM stability:	0.994 ? 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):

12.9

Half-life (T1/2):

1.093

ADMET: Toxicity

hERG Blockers:	0.177	hERG Blockers (10um):	0.729
Human Hepatotoxicity (H-HT):	0.666	Drug-induced Liver Injury (DILI):	0.066
AMES Toxicity:	0.16	Rat Oral Acute Toxicity:	0.216
Maximum Recommended Daily Dose:	0.296	Skin Sensitization:	0.991
Carcinogencity:	0.158	Eye Corrosion:	0.015
Eye Irritation:	0.907	Respiratory Toxicity:	0.95
Drug-induced Neurotoxicity:	0.27	Ototoxicity:	0.565
Hematotoxicity:	0.198	Drug-induced Nephrotoxicity:	0.356
Genotoxicity:	0.116	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.567	Hek293 Cytotoxicity:	0.252
BCF:	2.017 ? 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:	5.372 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.007 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.92 ? 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
NPO27847	Suillus granulatus	Species	Suillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575963]
NPO27847	Suillus granulatus	Species	Suillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1294697]
NPO27847	Suillus granulatus	Species	Suillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2607355]
NPO27847	Suillus granulatus	Species	Suillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2809609]
NPO27847	Suillus granulatus	Species	Suillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27847	Suillus granulatus	Species	Suillaceae	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	8

Activity Type	# Activity
Organism	8

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
NPT172	Organism	Proteus mirabilis	Proteus mirabilis	MIC	>	100.0	ug.mL-1	PMID[19880317]
NPT4678	Organism	Hafnia alvei	Hafnia alvei	MIC	>	100.0	ug.mL-1	PMID[22487595]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	>	100.0	ug.mL-1	PMID[11277768]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	100.0	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100.0	ug.mL-1	PMID[24576210]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	>	100.0	ug.mL-1	PMID[23395633]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[7411550]
NPT1843	Organism	Aeromonas hydrophila	Aeromonas hydrophila	MIC	>	100.0	ug.mL-1	PMID[9322367]

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 NPC476006 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	12543
0.1-0.2	33496
0.2-0.3	3423
0.3-0.4	304
0.4-0.5	61
0.5-0.6	25
0.6-0.7	3
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
0.661	Remote Similarity	NPC85895
0.6154	Remote Similarity	NPC37139
0.6154	Remote Similarity	NPC607595
0.5968	Remote Similarity	NPC74137
0.5862	Remote Similarity	NPC474920
0.5857	Remote Similarity	NPC488435
0.5781	Remote Similarity	NPC478288
0.5714	Remote Similarity	NPC488436
0.5692	Remote Similarity	NPC212965
0.5606	Remote Similarity	NPC483636
0.5538	Remote Similarity	NPC82503
0.5522	Remote Similarity	NPC600342
0.55	Remote Similarity	NPC474864
0.5469	Remote Similarity	NPC474616
0.5385	Remote Similarity	NPC474481
0.5323	Remote Similarity	NPC142530
0.5303	Remote Similarity	NPC601185
0.5303	Remote Similarity	NPC604281
0.5231	Remote Similarity	NPC233059
0.5231	Remote Similarity	NPC218753
0.5231	Remote Similarity	NPC601175
0.5224	Remote Similarity	NPC485470
0.5147	Remote Similarity	NPC120638
0.5143	Remote Similarity	NPC471587
0.5143	Remote Similarity	NPC241976
0.5079	Remote Similarity	NPC476165
0.5065	Remote Similarity	NPC488431
0.5065	Remote Similarity	NPC488432

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476006 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3169
0.1-0.2	5926
0.2-0.3	49
0.3-0.4	5
0.4-0.5	0
0.5-0.6	1
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
0.5077	Remote Similarity	NPD6671	Approved

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