NPASS Compound

Natural Product: NPC127894

Natural Product ID	NPC127894
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Oncostemonol D
IUPAC Name	5-[(Z)-16-(3-hydroxy-5-methoxyphenyl)hexadec-8-enyl]benzene-1,3-diol
Synonyms	oncostemonol D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL464027
PubChem CID	11744712
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 75 76 0 0 0 0 0 0 0 0999 V2000 6.7388 1.1299 4.2190 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3251 1.8783 3.2045 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5418 1.4892 1.9110 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1623 0.2288 1.4999 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3852 -0.1547 0.1918 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9653 -1.5176 -0.2193 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5358 -1.5275 -0.7249 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5795 -1.0545 0.3435 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1240 -1.0631 -0.1443 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9276 -0.1858 -1.3079 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5703 -0.0667 -1.8564 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8359 -1.1634 -2.4843 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5238 -2.3563 -1.7175 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7174 -2.7117 -1.4326 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8964 -1.9505 -1.8506 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7001 -1.5091 -0.6040 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8787 -0.7399 -1.1157 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7229 -0.2358 0.0659 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2294 -1.3738 0.8808 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0583 -0.9745 2.0380 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3603 -0.3658 1.8055 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5445 0.8426 1.0559 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0386 0.8015 -0.2532 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2271 1.9291 -0.9974 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9389 3.1590 -0.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4486 3.2167 0.8021 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2528 2.1052 1.5631 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1512 4.4604 1.3273 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7238 1.8224 -2.2994 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9803 0.7024 -0.7074 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3774 1.9867 -0.3246 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1451 2.3471 0.9848 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9794 2.8727 -1.2080 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2279 1.8125 4.9619 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9745 0.4160 3.9153 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5411 0.5514 4.7628 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6968 -0.4327 2.2178 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5974 -1.7957 -1.1017 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1423 -2.2770 0.5675 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2595 -2.5735 -0.9657 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5239 -0.8939 -1.6342 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6268 -1.7819 1.1775 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7793 -0.0103 0.6496 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7617 -2.0696 -0.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5508 -0.6096 0.7226 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6108 -0.5005 -2.1703 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2737 0.8637 -1.0160 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5392 0.8276 -2.5988 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8559 0.3771 -1.0468 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5562 -1.5070 -3.3620 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0220 -0.7933 -3.1120 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3232 -3.0600 -1.3755 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8558 -3.6486 -0.8387 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7152 -1.0272 -2.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6213 -2.5764 -2.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1002 -0.8876 0.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9854 -2.4730 -0.1241 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5753 0.1135 -1.7399 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5517 -1.3783 -1.7460 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4684 0.4205 -0.3675 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9850 0.3771 0.6994 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3416 -1.9868 1.2090 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7934 -2.0688 0.1818 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4398 -0.3299 2.7582 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1990 -1.9142 2.6628 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0041 -1.1767 1.2880 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9578 -0.2502 2.7748 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2799 -0.1559 -0.6912 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0823 4.0693 -1.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8648 2.1960 2.5780 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7968 5.1356 1.6650 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4319 2.5270 -2.9687 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1669 0.4232 -1.7462 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4385 3.3325 1.3164 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8168 2.7146 -2.1946 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 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 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 24 29 1 0 5 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 32 3 1 0 27 22 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 10 46 1 0 10 47 1 0 11 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 13 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 17 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 19 62 1 0 19 63 1 0 20 64 1 0 20 65 1 0 21 66 1 0 21 67 1 0 23 68 1 0 25 69 1 0 27 70 1 0 28 71 1 0 29 72 1 0 30 73 1 0 32 74 1 0 33 75 1 0 M END

Standard InCHIKey	NJAYBTLRHRIKOW-IHWYPQMZSA-N
Standard InCHI	InChI=1S/C29H42O4/c1-33-29-21-25(20-28(32)23-29)17-15-13-11-9-7-5-3-2-4-6-8-10-12-14-16-24-18-26(30)22-27(31)19-24/h2-3,18-23,30-32H,4-17H2,1H3/b3-2-
SMILES	COc1cc(CCCCCCC/C=CCCCCCCCc2cc(cc(c2)O)O)cc(c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.31	Volume:	509.733 ? Van der Waals volume.
Dense:	0.891	LogP:	8.284 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.745 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.719 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	13.0
TPSA:	69.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.168	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.557	Fsp³:	0.517
MCE-18:	12.0 ? 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:	0.939	Fluc inhibitor:	0.281 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.364 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.654	Promiscuous compounds:	0.051

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.165	MDCK Permeability:	-4.707
Pgp-inhibitor:	0.918	Pgp-substrate:	0.0
PAMPA:	0.0 ? 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%):	0.845	30% Bioavailability (F30%):	0.915
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.69
Plasma Protein Binding (PPB):	98.945%	Volume Distribution (VD):	0.4
Fu:	0.337% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.802
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.968
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.52	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.983	CYP2C19-substrate:	0.994
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.987	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.011	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.897 ? 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):

3.1

Half-life (T1/2):

1.355

ADMET: Toxicity

hERG Blockers:	0.818	hERG Blockers (10um):	0.904
Human Hepatotoxicity (H-HT):	0.385	Drug-induced Liver Injury (DILI):	0.005
AMES Toxicity:	0.252	Rat Oral Acute Toxicity:	0.114
Maximum Recommended Daily Dose:	0.795	Skin Sensitization:	1.0
Carcinogencity:	0.106	Eye Corrosion:	0.79
Eye Irritation:	0.994	Respiratory Toxicity:	0.773
Drug-induced Neurotoxicity:	0.034	Ototoxicity:	0.153
Hematotoxicity:	0.01	Drug-induced Nephrotoxicity:	0.242
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.087
A549 Cytotoxicity:	0.945	Hek293 Cytotoxicity:	0.964
BCF:	1.421 ? 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:	5.409 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.605 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.467 ? 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
NPO33313	oncostemon bojerianum	Species	n.a.	n.a.	leaves	Madagascar rainforest	n.a.	PMID[12444688]

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	10.0	ug.mL-1	PMID[10775404]

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 NPC127894 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	23482
0.1-0.2	22340
0.2-0.3	3709
0.3-0.4	225
0.4-0.5	49
0.5-0.6	16
0.6-0.7	25
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470759
0.907	High Similarity	NPC219070
0.8605	High Similarity	NPC114064
0.8298	Intermediate Similarity	NPC15860
0.8	Intermediate Similarity	NPC140521
0.72	Intermediate Similarity	NPC249836
0.6977	Remote Similarity	NPC470700
0.6977	Remote Similarity	NPC54844
0.6977	Remote Similarity	NPC39097
0.6977	Remote Similarity	NPC302681
0.6977	Remote Similarity	NPC118286
0.6977	Remote Similarity	NPC109691
0.6889	Remote Similarity	NPC168657
0.6667	Remote Similarity	NPC53051
0.6667	Remote Similarity	NPC24404
0.6667	Remote Similarity	NPC313030
0.6667	Remote Similarity	NPC39664
0.6522	Remote Similarity	NPC146798
0.6522	Remote Similarity	NPC222522
0.6522	Remote Similarity	NPC106396
0.6522	Remote Similarity	NPC94351
0.6522	Remote Similarity	NPC168303
0.6122	Remote Similarity	NPC71002
0.6122	Remote Similarity	NPC10588
0.6122	Remote Similarity	NPC302219
0.6122	Remote Similarity	NPC242342
0.6122	Remote Similarity	NPC249828
0.6122	Remote Similarity	NPC85479
0.6	Remote Similarity	NPC470699
0.6	Remote Similarity	NPC78446
0.6	Remote Similarity	NPC72947
0.5893	Remote Similarity	NPC473221
0.58	Remote Similarity	NPC284011
0.5581	Remote Similarity	NPC246056
0.5577	Remote Similarity	NPC470161
0.5357	Remote Similarity	NPC305603
0.5357	Remote Similarity	NPC61033
0.5294	Remote Similarity	NPC166761
0.5238	Remote Similarity	NPC480163
0.5217	Remote Similarity	NPC294186
0.5217	Remote Similarity	NPC147310
0.5217	Remote Similarity	NPC137415
0.5217	Remote Similarity	NPC166313
0.5217	Remote Similarity	NPC192032
0.5217	Remote Similarity	NPC24407
0.5217	Remote Similarity	NPC11280
0.5161	Remote Similarity	NPC29577

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC127894 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5084
0.1-0.2	3947
0.2-0.3	115
0.3-0.4	4
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