NPASS Compound

Natural Product: NPC189513

Natural Product ID	NPC189513
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	12-Deacetyl-12-Epi-Deoxoscalarin
IUPAC Name	(1R,5aS,5bR,7aS,11aS,11bR,13R,13aS,13bS)-5b,8,8,11a,13a-pentamethyl-1,3,5,5a,6,7,7a,9,10,11,11b,12,13,13b-tetradecahydrophenanthro[1,2-g][2]benzofuran-1,13-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL495273
PubChem CID	10548337
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001552] Sesterterpenoids [CHEMONTID:0002883] Scalarane sesterterpenoids

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 68 72 0 0 0 0 0 0 0 0999 V2000 -4.7549 -0.8830 0.7205 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9374 -0.0414 -0.2187 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4126 -0.4318 -1.6329 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2253 1.4268 -0.0858 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9596 2.1995 0.2634 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3337 1.4637 1.4302 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7444 0.1386 1.0590 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9742 -0.8167 2.1784 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4811 -0.2937 -0.2090 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0761 -1.6695 -0.6705 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6327 -1.6057 -1.0515 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2507 -0.9626 -0.0170 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6484 -2.0434 0.9575 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4574 -0.4448 -0.8030 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9668 -1.4137 -1.8001 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3069 -0.9561 -2.2671 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8941 0.1408 -1.8967 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1803 0.8182 -2.1917 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3687 1.8191 -1.2883 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3871 1.8379 -0.3360 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2496 1.0943 -0.9179 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5075 0.1722 0.0631 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5669 -0.8407 0.5057 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0316 0.9064 1.2455 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6380 0.7287 1.6836 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3105 0.2536 0.6324 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8689 0.6460 2.3654 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9811 3.1871 -0.1923 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8265 -0.4627 1.7462 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4515 -1.9311 0.6794 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8259 -0.8745 0.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6358 -0.1474 -2.3496 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6697 -1.5016 -1.6514 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3586 0.1310 -1.8113 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9990 1.6341 0.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6175 1.8940 -1.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2963 2.3662 -0.5788 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3064 3.1798 0.6718 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7003 2.1632 1.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2011 1.2593 2.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0889 -1.0407 2.8028 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3856 -1.7998 1.8831 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7242 -0.3945 2.8918 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0632 0.3917 -1.0140 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6466 -1.8240 -1.6356 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3626 -2.4887 -0.0263 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5777 -1.0035 -2.0012 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2671 -2.6417 -1.2176 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2290 -1.7051 1.8108 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2359 -2.6552 1.2509 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3045 -2.7802 0.4093 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9898 0.3958 -1.4079 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9707 -2.4732 -1.4849 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3203 -1.4029 -2.7293 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8139 -1.6111 -2.9751 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0503 1.2978 -3.2058 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0306 0.1132 -2.2804 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7060 1.5222 0.6688 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4939 1.6851 -1.4475 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5132 -1.0028 1.6094 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4624 -1.8106 0.0352 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5972 -0.4825 0.3136 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2434 2.0066 1.0648 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2600 1.7062 2.0616 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5959 0.0624 2.5918 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3178 1.0639 -0.1615 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3821 1.0396 3.1477 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1335 3.6915 -1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 1 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 20 28 1 0 9 2 1 0 26 12 1 0 26 7 1 0 22 14 1 0 21 17 1 0 1 29 1 0 1 30 1 0 1 31 1 0 3 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 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 6 10 45 1 0 10 46 1 0 11 47 1 0 11 48 1 0 13 49 1 0 13 50 1 0 13 51 1 0 14 52 1 6 15 53 1 0 15 54 1 0 16 55 1 0 18 56 1 0 18 57 1 0 20 58 1 1 21 59 1 6 23 60 1 0 23 61 1 0 23 62 1 0 24 63 1 6 25 64 1 0 25 65 1 0 26 66 1 6 27 67 1 0 28 68 1 0 M END

Standard InCHIKey	TVZPMYDGQOHLDW-VKYCOJTLSA-N
Standard InCHI	InChI=1S/C25H40O3/c1-22(2)10-6-11-23(3)16(22)9-12-24(4)17-8-7-15-14-28-21(27)20(15)25(17,5)19(26)13-18(23)24/h7,16-21,26-27H,6,8-14H2,1-5H3/t16-,17-,18+,19+,20+,21+,23-,24-,25+/m0/s1
SMILES	CC1(C)CCC[C@@]2(C)[C@H]1CC[C@@]1(C)[C@@H]3CC=C4CO[C@H]([C@@H]4[C@@]3(C)[C@@H](C[C@H]21)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	388.3	Volume:	421.908 ? Van der Waals volume.
Dense:	0.92	LogP:	3.695 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.571 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.674 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	25.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.579	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.994	Fsp³:	0.92
MCE-18:	93.5 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.523	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.248	Promiscuous compounds:	0.036

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.056	MDCK Permeability:	-4.799
Pgp-inhibitor:	0.845	Pgp-substrate:	0.009
PAMPA:	0.06 ? 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):	0.003
20% Bioavailability (F20%):	0.054	30% Bioavailability (F30%):	0.107
50% Bioavailability (F50%):	0.885

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.839	MRP1:	0.539
Plasma Protein Binding (PPB):	97.407%	Volume Distribution (VD):	0.313
Fu:	4.049% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.67
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.027	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.287
CYP2D6-inhibitor:	0.881	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.398
HLM stability:	0.617 ? 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):

10.967

Half-life (T1/2):

1.629

ADMET: Toxicity

hERG Blockers:	0.201	hERG Blockers (10um):	0.522
Human Hepatotoxicity (H-HT):	0.45	Drug-induced Liver Injury (DILI):	0.351
AMES Toxicity:	0.158	Rat Oral Acute Toxicity:	0.238
Maximum Recommended Daily Dose:	0.862	Skin Sensitization:	0.869
Carcinogencity:	0.71	Eye Corrosion:	0.022
Eye Irritation:	0.607	Respiratory Toxicity:	0.885
Drug-induced Neurotoxicity:	0.082	Ototoxicity:	0.677
Hematotoxicity:	0.25	Drug-induced Nephrotoxicity:	0.556
Genotoxicity:	0.112	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.058	Hek293 Cytotoxicity:	0.491
BCF:	2.217 ? 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:	4.404 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.585 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.157 ? 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
NPO33445	glossodoris atromarginata	Species	Chromodorididae	Eukaryota	n.a.	n.a.	n.a.	PMID[10543894]
NPO33333	hyrtios erecta	Species	Thorectidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[11809054]
NPO33333	hyrtios erecta	Species	Thorectidae	Eukaryota	n.a.	Indian Ocean	n.a.	PMID[16124771]
NPO33333	hyrtios erecta	Species	Thorectidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[16378375]
NPO33333	hyrtios erecta	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9584401]
NPO33333	hyrtios erecta	Species	Thorectidae	Eukaryota	n.a.	Maldives	n.a.	PMID[9873492]

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
NPT168	Cell line	P388	Mus musculus	IC50	>	1.0	ug.mL-1	PMID[20677781]

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 NPC189513 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	21060
0.1-0.2	24644
0.2-0.3	3809
0.3-0.4	294
0.4-0.5	29
0.5-0.6	10
0.6-0.7	7
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
0.7818	Intermediate Similarity	NPC135224
0.7705	Intermediate Similarity	NPC161527
0.7288	Intermediate Similarity	NPC222161
0.6897	Remote Similarity	NPC76266
0.6731	Remote Similarity	NPC17550
0.661	Remote Similarity	NPC12046
0.6557	Remote Similarity	NPC100892
0.6129	Remote Similarity	NPC110496
0.6094	Remote Similarity	NPC228251
0.6094	Remote Similarity	NPC477972
0.5932	Remote Similarity	NPC606859
0.5455	Remote Similarity	NPC157441
0.5352	Remote Similarity	NPC477968
0.5278	Remote Similarity	NPC20113
0.5077	Remote Similarity	NPC61369
0.5077	Remote Similarity	NPC5532
0.5077	Remote Similarity	NPC469545
0.5075	Remote Similarity	NPC275539
0.5075	Remote Similarity	NPC471207
0.5075	Remote Similarity	NPC189075

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC189513 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7453
0.1-0.2	1605
0.2-0.3	92
0.3-0.4	0
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