NPASS Compound

Natural Product: NPC23667

Natural Product ID	NPC23667
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Guttiferone I
IUPAC Name	n.a.
Synonyms	Guttiferone I
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL445689
PubChem CID	n.a.
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 2D 107109 0 0 0 0 0 0 0 0999 V2000 9.5435 -6.7493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3944 -5.7851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6549 -4.3079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5058 -3.3437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3567 -2.3795 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -1.4153 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -1.9284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 -6.4952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2500 3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7500 3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5000 5.1962 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2500 6.4952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2735 0.1929 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4895 2.7762 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 1.8121 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5691 2.3251 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9786 2.8381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1277 1.8739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5372 2.3870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8672 0.3967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4681 0.0619 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9849 -6.2981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5793 -7.8983 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5076 -5.6002 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6925 -7.7135 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0644 -3.7948 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4700 -2.1946 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4087 -4.3667 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3209 -1.2304 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3926 -3.5286 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5377 -3.4056 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8321 -2.2222 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4660 0.2938 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7580 0.8169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0865 -1.9801 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6715 -2.7970 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2010 -3.3481 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9991 -2.5459 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 -3.8971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9510 -7.2452 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5490 -5.7452 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -7.7942 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -6.6962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1828 -3.7073 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -5.1962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 2.5981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 5.1962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5000 0.0000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7500 1.2990 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0000 5.1962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1192 3.1841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9419 2.1847 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 3.8971 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9510 7.2452 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5490 5.7452 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 7.7942 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 6.6962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3630 3.7407 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 5.1962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9240 3.2148 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0068 2.8810 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4111 4.2742 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8222 3.2736 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8406 0.4756 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9065 0.8635 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0560 3.7346 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2391 4.3153 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0503 0.9774 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0242 3.7965 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9468 2.9000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3652 0.3183 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4328 0.8353 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9719 -1.0996 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 -2.5981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9026 -0.3767 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9702 0.1403 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0783 1.4322 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4979 -7.7077 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3038 -4.9616 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5753 -6.8111 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 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 1 0 10 11 1 0 11 12 1 6 12 13 1 0 13 14 2 3 14 15 1 0 14 16 1 0 11 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 24 28 1 0 18 29 1 0 29 30 2 0 29 31 1 0 31 32 1 6 32 33 1 0 33 34 2 3 34 35 1 0 34 36 1 0 31 37 1 0 37 38 2 0 31 39 1 0 39 40 1 1 39 41 1 0 41 42 1 0 42 43 1 0 43 44 2 3 44 45 1 0 44 46 1 0 17 47 1 0 6 48 1 0 2 49 1 0 39 9 1 0 37 11 1 0 26 21 1 0 1 50 1 0 1 51 1 0 1 52 1 0 3 53 1 0 4 54 1 0 4 55 1 0 5 56 1 0 5 57 1 0 7 58 1 0 8 59 1 0 8 60 1 0 9 61 1 6 10 62 1 0 10 63 1 0 12 64 1 0 12 65 1 0 13 66 1 0 15 67 1 0 15 68 1 0 15 69 1 0 16 70 1 0 16 71 1 0 16 72 1 0 22 73 1 0 23 74 1 0 26 75 1 0 27 76 1 0 28 77 1 0 32 78 1 0 32 79 1 0 33 80 1 0 35 81 1 0 35 82 1 0 35 83 1 0 36 84 1 0 36 85 1 0 36 86 1 0 40 87 1 0 40 88 1 0 40 89 1 0 41 90 1 0 41 91 1 0 42 92 1 0 42 93 1 0 43 94 1 0 45 95 1 0 45 96 1 0 45 97 1 0 46 98 1 0 46 99 1 0 46100 1 0 47101 1 0 48102 1 0 48103 1 0 48104 1 0 49105 1 0 49106 1 0 49107 1 0 M END

Standard InCHIKey	XIKKSUTXFFVDEF-VOWDTJCUSA-N
Standard InCHI	InChI=1S/C43H58O6/c1-27(2)13-11-15-31(9)16-18-33-26-42(23-20-29(5)6)38(47)36(37(46)32-17-19-34(44)35(45)25-32)39(48)43(40(42)49,24-21-30(7)8)41(33,10)22-12-14-28(3)4/h13-14,16-17,19-21,25,33,44-45,47H,11-12,15,18,22-24,26H2,1-10H3/b31-16+/t33-,41+,42-,43+/m0/s1
SMILES	CC(=CCC/C(=C/C[C@H]1C[C@@]2(CC=C(C)C)C(=C(C(=O)c3ccc(c(c3)O)O)C(=O)[C@](CC=C(C)C)(C2=O)[C@]1(C)CCC=C(C)C)O)/C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	670.42	Volume:	747.718 ? Van der Waals volume.
Dense:	0.897	LogP:	8.187 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	5.557 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.911 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	24.0
TPSA:	111.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.06	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.719	Fsp³:	0.512
MCE-18:	100.923 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.998	Fluc inhibitor:	0.137 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.032 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.556 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.608	Promiscuous compounds:	0.191

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.742	MDCK Permeability:	-4.642
Pgp-inhibitor:	0.049	Pgp-substrate:	0.0
PAMPA:	0.453 ? 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%):	0.004	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.997
Plasma Protein Binding (PPB):	92.363%	Volume Distribution (VD):	0.044
Fu:	9.127% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.664	BCRP inhibitor:	0.001
BSEP inhibitor:	0.267

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.687	CYP2C19-substrate:	0.773
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.973	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	1.0 ? 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):

4.347

Half-life (T1/2):

1.386

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.274
Human Hepatotoxicity (H-HT):	0.794	Drug-induced Liver Injury (DILI):	0.415
AMES Toxicity:	0.192	Rat Oral Acute Toxicity:	0.694
Maximum Recommended Daily Dose:	0.226	Skin Sensitization:	0.999
Carcinogencity:	0.26	Eye Corrosion:	0.0
Eye Irritation:	0.018	Respiratory Toxicity:	0.939
Drug-induced Neurotoxicity:	0.135	Ototoxicity:	0.946
Hematotoxicity:	0.448	Drug-induced Nephrotoxicity:	0.952
Genotoxicity:	0.987	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.668	Hek293 Cytotoxicity:	0.137
BCF:	1.706 ? 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:	6.169 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	8.498 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	8.599 ? 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
NPO26536	Garcinia humilis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15844964]
NPO15264	Garcinia paucinervis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20594858]
NPO26536	Garcinia humilis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15264	Garcinia paucinervis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15264	Garcinia paucinervis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26536	Garcinia humilis	Species	Clusiaceae	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
IC50	2
Ratio IC50	1

Activity Type	# Activity
Individual protein	2
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1794	Individual protein	LXR-alpha	Homo sapiens	IC50	=	3400.0	nM	PMID[25819096]
NPT1746	Individual protein	LXR-beta	Homo sapiens	IC50	>	15000.0	nM	PMID[25819096]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6536	Others	Liver X receptor (LXR alpha AND LXR beta)	Homo sapiens	Ratio IC50	=	5.0	n.a.	PMID[25819096]

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 NPC23667 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	7969
0.1-0.2	39132
0.2-0.3	2606
0.3-0.4	80
0.4-0.5	23
0.5-0.6	19
0.6-0.7	9
0.7-0.8	0
0.8-0.85	7
0.85-0.9	8
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC157284
0.9552	High Similarity	NPC5014
0.8939	High Similarity	NPC289358
0.8939	High Similarity	NPC4289
0.8939	High Similarity	NPC42384
0.863	High Similarity	NPC482617
0.863	High Similarity	NPC482616
0.8592	High Similarity	NPC25736
0.8551	High Similarity	NPC114333
0.8551	High Similarity	NPC28592
0.8429	Intermediate Similarity	NPC473479
0.8429	Intermediate Similarity	NPC50615
0.8429	Intermediate Similarity	NPC141650
0.8243	Intermediate Similarity	NPC482618
0.8169	Intermediate Similarity	NPC165191
0.8169	Intermediate Similarity	NPC177501
0.8028	Intermediate Similarity	NPC51531
0.7808	Intermediate Similarity	NPC482621
0.7639	Intermediate Similarity	NPC198803
0.7286	Intermediate Similarity	NPC149773
0.6933	Remote Similarity	NPC48949
0.6627	Remote Similarity	NPC482620
0.6538	Remote Similarity	NPC30846
0.6364	Remote Similarity	NPC46242
0.6364	Remote Similarity	NPC91887
0.6364	Remote Similarity	NPC93556
0.6329	Remote Similarity	NPC469857
0.6329	Remote Similarity	NPC245760
0.6282	Remote Similarity	NPC297797
0.5976	Remote Similarity	NPC471971
0.5976	Remote Similarity	NPC471972
0.5976	Remote Similarity	NPC469855
0.5854	Remote Similarity	NPC294330
0.5854	Remote Similarity	NPC479151
0.5732	Remote Similarity	NPC479148
0.5714	Remote Similarity	NPC469856
0.5647	Remote Similarity	NPC471970
0.5641	Remote Similarity	NPC473779
0.56	Remote Similarity	NPC259400
0.56	Remote Similarity	NPC130591
0.56	Remote Similarity	NPC234637
0.5595	Remote Similarity	NPC469854
0.5595	Remote Similarity	NPC482619
0.5412	Remote Similarity	NPC603871
0.5287	Remote Similarity	NPC479146
0.5172	Remote Similarity	NPC237441
0.5119	Remote Similarity	NPC473527
0.5063	Remote Similarity	NPC611064

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC23667 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3983
0.1-0.2	5102
0.2-0.3	65
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