NPASS Compound

Natural Product: NPC299734

Natural Product ID	NPC299734
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Macrocarpal C
IUPAC Name	5-[(1R)-1-[(1aR,4aR,7S,7aR,7bR)-1,1,7-trimethyl-4-methylidene-1a,2,3,4a,5,6,7a,7b-octahydrocyclopropa[h]azulen-7-yl]-3-methylbutyl]-2,4,6-trihydroxybenzene-1,3-dicarbaldehyde
Synonyms	Macrocarpal C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL466994
PubChem CID	454459
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0001781] Aromadendrane sesquiterpenoids [CHEMONTID:0003562] 5,10-cycloaromadendrane 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 71 74 0 0 0 0 0 0 0 0999 V2000 3.1009 1.9298 -1.8745 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1892 2.0974 -0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2044 3.1385 -0.0150 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8551 2.3244 0.2712 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9340 1.1500 0.0259 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4566 -0.1084 0.5497 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7103 -0.3752 1.8928 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1860 -1.5786 2.3560 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4375 -1.8127 3.7889 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5449 -2.2694 4.5507 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4465 -2.6118 1.5051 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2145 -2.4021 0.1651 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4883 -3.4952 -0.7558 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5542 -4.3075 -1.0078 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7396 -1.1986 -0.2863 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5367 -1.0870 -1.6709 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9313 -3.8355 1.9849 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4848 0.6039 2.8299 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5233 1.4486 0.2357 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8694 1.9086 1.6323 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7729 2.7162 -0.6310 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2215 2.6571 -1.0243 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6081 1.2536 -0.9448 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0025 0.6742 -2.2251 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5664 1.1986 -3.3397 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8890 -0.5538 -2.3245 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1760 -1.5553 -1.4234 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2341 -1.2480 0.0171 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1483 -0.4608 0.6430 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4543 0.4353 -0.3169 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0820 -1.8745 0.8251 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2208 -2.8758 0.1431 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5690 -2.4073 2.1903 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8949 2.5724 -2.3463 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2967 0.9176 -2.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1334 2.2664 -2.3042 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5955 1.1153 0.0091 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7423 4.0993 0.2901 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8836 2.8183 0.8044 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8734 3.3490 -0.8892 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9050 2.6395 1.3076 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4069 3.1993 -0.2889 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0715 1.0267 -1.1179 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4205 -1.5743 4.1515 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4573 -3.5927 -1.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2834 -1.2614 -2.3326 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2775 -4.5502 1.3839 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8984 0.3780 3.6461 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7794 2.5855 1.5214 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0549 1.1231 2.3573 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0706 2.6438 1.9341 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5102 3.6309 -0.0937 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1698 2.5952 -1.5438 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4442 3.1930 -1.9600 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7645 3.2818 -0.2359 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5236 1.1969 -0.2802 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9266 2.0370 -3.4393 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8912 0.7281 -4.2901 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9117 -0.9533 -3.3374 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8508 -0.2797 -1.8891 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1857 -1.7028 -1.8668 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7264 -2.5286 -1.5896 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2538 -1.2737 0.4527 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5492 0.1494 1.5214 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9595 -0.1663 -1.1087 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7352 -2.5501 -0.7796 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8696 -3.7880 -0.0275 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4661 -3.2256 0.8781 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7361 -2.5772 2.8752 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2788 -1.6820 2.6524 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1598 -3.3187 1.9754 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 2 0 7 8 1 0 8 9 1 0 9 10 2 0 8 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 12 15 2 0 15 16 1 0 11 17 1 0 7 18 1 0 5 19 1 0 19 20 1 1 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 31 33 1 0 15 6 1 0 30 19 1 0 30 23 1 0 31 28 1 0 1 34 1 0 1 35 1 0 1 36 1 0 2 37 1 0 3 38 1 0 3 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 5 43 1 6 9 44 1 0 13 45 1 0 16 46 1 0 17 47 1 0 18 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 21 52 1 0 21 53 1 0 22 54 1 0 22 55 1 0 23 56 1 1 25 57 1 0 25 58 1 0 26 59 1 0 26 60 1 0 27 61 1 0 27 62 1 0 28 63 1 1 29 64 1 1 30 65 1 6 32 66 1 0 32 67 1 0 32 68 1 0 33 69 1 0 33 70 1 0 33 71 1 0 M END

Standard InCHIKey	IEWHEHWXBLPFER-HUCVFKCKSA-N
Standard InCHI	InChI=1S/C28H38O5/c1-14(2)11-20(21-25(32)17(12-29)24(31)18(13-30)26(21)33)28(6)10-9-16-15(3)7-8-19-23(22(16)28)27(19,4)5/h12-14,16,19-20,22-23,31-33H,3,7-11H2,1-2,4-6H3/t16-,19+,20-,22+,23+,28+/m0/s1
SMILES	CC(C)C[C@@H](c1c(c(C=O)c(c(C=O)c1O)O)O)[C@@]1(C)CC[C@H]2C(=C)CC[C@@H]3[C@H]([C@H]12)C3(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.27	Volume:	486.751 ? Van der Waals volume.
Dense:	0.933	LogP:	5.584 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.198 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.948 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	22.0
TPSA:	94.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.351	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.946	Fsp³:	0.643
MCE-18:	106.478 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.748	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.062 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.336	Promiscuous compounds:	0.146

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.448	MDCK Permeability:	-4.892
Pgp-inhibitor:	0.992	Pgp-substrate:	0.0
PAMPA:	0.005 ? 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):	0.002
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.584
50% Bioavailability (F50%):	0.945

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.05	MRP1:	0.963
Plasma Protein Binding (PPB):	98.019%	Volume Distribution (VD):	-0.009
Fu:	1.549% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.426
BSEP inhibitor:	0.988

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.896
CYP2C9-inhibitor:	0.765	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.197
HLM stability:	0.054 ? 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):

8.099

Half-life (T1/2):

0.847

ADMET: Toxicity

hERG Blockers:	0.023	hERG Blockers (10um):	0.408
Human Hepatotoxicity (H-HT):	0.441	Drug-induced Liver Injury (DILI):	0.12
AMES Toxicity:	0.149	Rat Oral Acute Toxicity:	0.306
Maximum Recommended Daily Dose:	0.622	Skin Sensitization:	0.9
Carcinogencity:	0.271	Eye Corrosion:	0.403
Eye Irritation:	0.988	Respiratory Toxicity:	0.908
Drug-induced Neurotoxicity:	0.119	Ototoxicity:	0.36
Hematotoxicity:	0.076	Drug-induced Nephrotoxicity:	0.109
Genotoxicity:	0.486	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.731	Hek293 Cytotoxicity:	0.619
BCF:	2.164 ? 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:	5.598 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.459 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.034 ? 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
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	fruit	n.a.	PMID[18020353]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22934600]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[23678820]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27142786]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[30543429]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[30848923]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35108453]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36903935]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37047195]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37179510]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38263385]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38380569]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39064968]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39592457]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[8864235]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7175	Eucalyptus robusta	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15388	Eucalyptus globulus	Species	Myrtaceae	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	10
Inhibition	3
IC50	2

Activity Type	# Activity
Organism	10
Others	3
Non-molecular	2

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
NPT878	Organism	Streptococcus mutans	Streptococcus mutans	MIC	=	0.39	ug.mL-1	PMID[16441079]
NPT4829	Organism	Prevotella melaninogenica	Prevotella melaninogenica	MIC	=	1.56	ug.mL-1	PMID[11575965]
NPT1128	Organism	Prevotella intermedia	Prevotella intermedia	MIC	=	0.39	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT1484	Organism	Fusobacterium nucleatum	Fusobacterium nucleatum	MIC	=	0.78	ug.mL-1	PMID[17958396]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	<	10000.0	nM	PMID[27142786]
NPT5408	Organism	Capnocytophaga ochracea	Capnocytophaga ochracea	MIC	=	0.39	ug.mL-1	PMID[9599262]
NPT1127	Organism	Porphyromonas gingivalis	Porphyromonas gingivalis	MIC	=	0.2	ug.mL-1	PMID[11858748]
NPT2	Others	Unspecified	n.a.	Inhibition	=	98.9	%	PMID[26316467]
NPT2	Others	Unspecified	n.a.	Inhibition	=	92.6	%	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Inhibition	=	18.9	%	PMID[22440015]
NPT1483	Organism	Streptococcus sobrinus	Streptococcus sobrinus	MIC	=	1.56	ug.mL-1	PMID[18687007]
NPT1129	Organism	Actinomyces viscosus	Actinomyces viscosus	MIC	=	0.2	ug.mL-1	PMID[17279797]

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 NPC299734 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	13159
0.1-0.2	35879
0.2-0.3	760
0.3-0.4	28
0.4-0.5	17
0.5-0.6	5
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488488
1.0	High Similarity	NPC605436
0.6441	Remote Similarity	NPC244640
0.6441	Remote Similarity	NPC279291
0.6441	Remote Similarity	NPC482103
0.6441	Remote Similarity	NPC488484
0.6441	Remote Similarity	NPC600251
0.6333	Remote Similarity	NPC482107
0.6129	Remote Similarity	NPC482102
0.6129	Remote Similarity	NPC488483
0.5714	Remote Similarity	NPC482105
0.5714	Remote Similarity	NPC482104
0.5645	Remote Similarity	NPC130028
0.5645	Remote Similarity	NPC474109
0.5455	Remote Similarity	NPC603742

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC299734 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5497
0.1-0.2	3631
0.2-0.3	22
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