NPASS Compound

Natural Product: NPC474358

Natural Product ID	NPC474358
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Calicoferol F
IUPAC Name	(1R,3aS,4S,5R,7aR)-1-[(E,2R)-5,6-dimethylhept-3-en-2-yl]-4-[2-(5-hydroxy-2-methylphenyl)ethyl]-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-5-ol
Synonyms	Calicoferol F
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465610
PubChem CID	10047332
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

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 74 76 0 0 0 0 0 0 0 0999 V2000 3.0269 2.8476 -0.7042 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2458 2.0192 -0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6464 1.1971 0.3428 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8979 0.5629 0.3178 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7150 0.7880 -0.7516 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3324 1.6217 -1.7963 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1056 2.2380 -1.7583 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9639 0.1420 -0.7574 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7463 0.7704 1.4360 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3072 -0.6351 1.3563 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5094 -1.1984 0.2581 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1519 -0.6494 0.1373 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7946 0.0728 -1.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7403 -0.0733 -1.2250 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1458 -0.7975 0.0759 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0449 -1.7459 0.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1942 -2.5331 1.3534 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5608 -3.1581 1.4931 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5376 -2.7274 0.4674 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8219 -3.0302 0.9863 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1210 -2.5379 -1.1397 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4700 -1.4115 -0.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8801 -2.1390 1.2523 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6295 -0.5963 -0.3742 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6899 0.7013 -0.3879 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9788 1.4070 -0.7968 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6800 2.2558 -2.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4512 2.2373 0.3605 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6830 1.3052 1.5516 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8375 2.8275 0.0632 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3132 2.7160 0.1072 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4842 2.7715 -1.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3720 3.9388 -0.5823 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1807 -0.0659 1.1158 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9842 1.7872 -2.6350 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7907 2.8851 -2.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8804 -0.8658 -0.9658 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8616 1.4313 1.4213 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2414 0.9870 2.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6594 -0.7858 2.3027 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1641 -1.3397 1.6243 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0063 -1.0347 -0.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8657 0.0027 0.9998 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3070 -0.2133 -2.0210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9314 1.1675 -0.9286 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1943 0.9036 -1.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9700 -0.6720 -2.1190 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9999 -0.0745 0.8835 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5802 -3.3396 1.4270 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0687 -1.8794 2.2309 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4376 -4.2591 1.4168 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9843 -3.0014 2.5278 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5264 -3.2760 -0.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7835 -3.4370 1.8657 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9241 -2.1898 -1.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2623 -3.6400 -0.8867 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7856 -2.5562 -1.7687 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4304 -2.3051 -0.7769 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8751 -1.6921 1.5852 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2296 -1.9739 2.1185 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0424 -3.2325 1.0981 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5378 -1.1568 -0.6658 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9189 1.4071 -0.1052 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6995 0.6044 -1.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3796 3.2835 -1.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8221 1.8758 -2.5847 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6012 2.3671 -2.6176 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7794 3.0468 0.6274 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7238 1.8987 2.4638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8728 0.5686 1.6047 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6458 0.7481 1.3377 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4099 2.8455 0.9984 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3549 2.1478 -0.6501 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7137 3.8458 -0.2978 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 2 0 5 6 1 0 6 7 2 0 5 8 1 0 3 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 16 21 1 0 15 22 1 0 22 23 1 0 22 24 1 0 24 25 2 3 25 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 28 30 1 0 7 2 1 0 19 11 1 0 16 12 1 0 1 31 1 0 1 32 1 0 1 33 1 0 4 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 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 0 14 47 1 0 15 48 1 0 17 49 1 0 17 50 1 0 18 51 1 0 18 52 1 0 19 53 1 0 20 54 1 0 21 55 1 0 21 56 1 0 21 57 1 0 22 58 1 0 23 59 1 0 23 60 1 0 23 61 1 0 24 62 1 0 25 63 1 0 26 64 1 0 27 65 1 0 27 66 1 0 27 67 1 0 28 68 1 0 29 69 1 0 29 70 1 0 29 71 1 0 30 72 1 0 30 73 1 0 30 74 1 0 M END

Standard InCHIKey	WPPVLVJCHIZUQE-FWJZWBEMSA-N
Standard InCHI	InChI=1S/C28H44O2/c1-18(2)19(3)7-8-21(5)25-13-14-26-24(27(30)15-16-28(25,26)6)12-10-22-17-23(29)11-9-20(22)4/h7-9,11,17-19,21,24-27,29-30H,10,12-16H2,1-6H3/b8-7+/t19?,21-,24+,25-,26+,27-,28-/m1/s1
SMILES	CC1=C(C=C(C=C1)O)CCC2C3CCC(C3(CCC2O)C)C(C)C=CC(C)C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	412.33	Volume:	474.209 ? Van der Waals volume.
Dense:	0.87	LogP:	6.891 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.993 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.822 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	17.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.477	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.318	Fsp³:	0.714
MCE-18:	74.25 ? 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:	0.852	Fluc inhibitor:	0.035 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.092 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.185	Promiscuous compounds:	0.067

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.044	MDCK Permeability:	-4.728
Pgp-inhibitor:	0.088	Pgp-substrate:	0.008
PAMPA:	0.043 ? 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):	0.0
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.012
50% Bioavailability (F50%):	0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.975	MRP1:	0.994
Plasma Protein Binding (PPB):	97.749%	Volume Distribution (VD):	0.14
Fu:	2.303% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.164
OATP1B3 inhibitor:	0.786	BCRP inhibitor:	0.007
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.027	CYP1A2-substrate:	0.134
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.88
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.253	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	0.044	CYP3A4-substrate:	0.988
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

13.605

Half-life (T1/2):

1.064

ADMET: Toxicity

hERG Blockers:	0.546	hERG Blockers (10um):	0.854
Human Hepatotoxicity (H-HT):	0.705	Drug-induced Liver Injury (DILI):	0.017
AMES Toxicity:	0.095	Rat Oral Acute Toxicity:	0.185
Maximum Recommended Daily Dose:	0.725	Skin Sensitization:	0.051
Carcinogencity:	0.117	Eye Corrosion:	0.0
Eye Irritation:	0.092	Respiratory Toxicity:	0.475
Drug-induced Neurotoxicity:	0.337	Ototoxicity:	0.963
Hematotoxicity:	0.063	Drug-induced Nephrotoxicity:	0.21
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.219	Hek293 Cytotoxicity:	0.694
BCF:	2.503 ? 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:	5.289 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.277 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.901 ? 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
NPO32639	muricella	Genus	Acanthogorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7595595]
NPO32639	muricella	Genus	Acanthogorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9834177]

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

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

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 NPC474358 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	10670
0.1-0.2	36355
0.2-0.3	2767
0.3-0.4	40
0.4-0.5	6
0.5-0.6	9
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC601488
0.9216	High Similarity	NPC474387
0.8364	Intermediate Similarity	NPC154511
0.8364	Intermediate Similarity	NPC608033
0.7368	Intermediate Similarity	NPC137496
0.7288	Intermediate Similarity	NPC257540
0.7119	Intermediate Similarity	NPC247858
0.6885	Remote Similarity	NPC611524
0.6557	Remote Similarity	NPC473974
0.6349	Remote Similarity	NPC68339
0.5909	Remote Similarity	NPC611030
0.5821	Remote Similarity	NPC611179
0.5606	Remote Similarity	NPC601566
0.5606	Remote Similarity	NPC607626
0.5522	Remote Similarity	NPC258366
0.5362	Remote Similarity	NPC610365
0.5352	Remote Similarity	NPC609225
0.5217	Remote Similarity	NPC610366
0.5211	Remote Similarity	NPC609139

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474358 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4577
0.1-0.2	4405
0.2-0.3	152
0.3-0.4	15
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