NPASS Compound

Natural Product: NPC67777

Natural Product ID	NPC67777
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Fokienagarofuran D
IUPAC Name	n.a.
Synonyms	Fokienagarofuran D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL487597
PubChem CID	11578600
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0002995] Pentacarboxylic acids and derivatives

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 100106 0 0 0 0 0 0 0 0999 V2000 -6.1690 2.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6436 0.8843 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8494 -0.0079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1641 0.6369 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6387 -0.7681 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6255 -2.2680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1050 -2.0206 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0590 -3.1781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5336 -4.5831 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5384 -2.9306 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0639 -1.5257 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5433 -1.2782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4973 -2.4357 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9719 -3.8407 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4925 -4.0882 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3199 -3.0066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0275 -2.2452 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3463 -0.0067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5599 0.8750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7734 1.7567 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1437 1.1466 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6568 -0.2629 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3572 2.0282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2004 3.5200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4140 4.4017 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7843 3.7916 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9411 2.2998 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7276 1.4181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1895 1.4851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5524 2.9405 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4734 3.9825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0081 3.7479 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8363 5.4380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7573 6.4800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1202 7.9354 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5621 8.3489 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6411 7.3069 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2782 5.8514 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8192 2.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5241 0.5932 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4057 1.8067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1454 3.2840 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8975 1.6499 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7792 2.8635 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2710 2.7067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8811 1.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9994 0.1228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5076 0.2796 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 1.0037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 -1.0037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5021 -3.6501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3389 3.7796 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5740 1.7639 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7641 2.8147 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0692 -1.2193 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1261 -3.6820 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7651 -0.0557 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0687 0.1267 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9768 -2.1883 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9259 -4.9982 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9670 -5.4931 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2739 -4.1641 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4919 -4.2574 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4697 -2.3367 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7169 2.3668 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2870 -0.4370 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9147 4.2926 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2572 5.8935 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9978 4.6733 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3114 1.6897 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8843 -0.0736 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3714 2.4088 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6846 6.0665 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0412 8.9774 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9249 9.8043 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0830 7.7203 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3572 4.8094 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2598 3.1372 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3322 3.5048 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 2.6401 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6899 2.0982 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0066 4.1492 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4201 3.6708 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2906 0.8232 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9230 -1.0591 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9458 -1.1112 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5054 2.0074 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5228 0.0196 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5304 2.2324 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5054 -2.0074 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5228 -0.0196 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3870 -2.1184 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0233 -5.0551 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9029 -3.1247 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8326 -4.3429 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 6 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 6 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 19 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 30 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 2 0 44 46 1 0 46 47 2 0 47 48 1 0 48 49 2 0 49 50 1 0 50 51 2 0 41 52 1 0 52 53 1 0 52 54 1 0 52 55 1 0 17 56 1 0 19 5 1 0 29 24 1 0 39 34 1 0 51 46 1 0 15 10 1 0 18 53 1 1 42 18 1 0 1 57 1 0 1 58 1 0 1 59 1 0 5 60 1 1 6 61 1 1 11 62 1 0 12 63 1 0 13 64 1 0 14 65 1 0 15 66 1 0 16 67 1 0 16 68 1 0 17 69 1 1 20 70 1 0 20 71 1 0 25 72 1 0 26 73 1 0 27 74 1 0 28 75 1 0 29 76 1 0 30 77 1 6 35 78 1 0 36 79 1 0 37 80 1 0 38 81 1 0 39 82 1 0 40 83 1 0 40 84 1 0 41 85 1 6 42 86 1 1 47 87 1 0 48 88 1 0 49 89 1 0 50 90 1 0 51 91 1 0 54 92 1 0 54 93 1 0 54 94 1 0 55 95 1 0 55 96 1 0 55 97 1 0 56 98 1 0 56 99 1 0 56100 1 0 M END

Standard InCHIKey	CZZSDKFRUYZLHU-DQSPPWPVSA-N
Standard InCHI	InChI=1S/C45H44O11/c1-28-25-35(53-40(48)31-19-11-6-12-20-31)38(52-29(2)46)44(27-51-39(47)30-17-9-5-10-18-30)36(54-41(49)32-21-13-7-14-22-32)26-34-37(45(28,44)56-43(34,3)4)55-42(50)33-23-15-8-16-24-33/h5-24,28,34-38H,25-27H2,1-4H3/t28-,34-,35+,36+,37-,38+,44-,45-/m1/s1
SMILES	CC(=O)O[C@H]1[C@@H](OC(=O)c2ccccc2)C[C@H]([C@@]23[C@]1(COC(=O)c1ccccc1)[C@@H](OC(=O)c1ccccc1)C[C@H]([C@H]3OC(=O)c1ccccc1)C(O2)(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	760.29	Volume:	778.853 ? Van der Waals volume.
Dense:	0.976	LogP:	5.295 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.332 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.437 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	43.0
TPSA:	140.73 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	0.0	Rings:	7.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.121	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.831	Fsp³:	0.356
MCE-18:	196.23 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.998	Fluc inhibitor:	0.159 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.615 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.254	Promiscuous compounds:	0.012

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.296	MDCK Permeability:	-4.71
Pgp-inhibitor:	0.999	Pgp-substrate:	0.026
PAMPA:	0.037 ? 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%):	0.0	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.778

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.997	MRP1:	1.0
Plasma Protein Binding (PPB):	96.538%	Volume Distribution (VD):	-0.43
Fu:	3.383% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.005
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.958
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

1.12

Half-life (T1/2):

1.164

ADMET: Toxicity

hERG Blockers:	0.227	hERG Blockers (10um):	0.872
Human Hepatotoxicity (H-HT):	0.018	Drug-induced Liver Injury (DILI):	0.98
AMES Toxicity:	0.125	Rat Oral Acute Toxicity:	0.012
Maximum Recommended Daily Dose:	0.242	Skin Sensitization:	0.989
Carcinogencity:	0.62	Eye Corrosion:	0.0
Eye Irritation:	0.019	Respiratory Toxicity:	0.007
Drug-induced Neurotoxicity:	0.872	Ototoxicity:	0.256
Hematotoxicity:	0.005	Drug-induced Nephrotoxicity:	0.627
Genotoxicity:	0.053	RPMI-8226 Immunitoxicity:	0.039
A549 Cytotoxicity:	0.71	Hek293 Cytotoxicity:	0.815
BCF:	0.826 ? 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:	4.826 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.809 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.877 ? 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
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	stem	n.a.	n.a.	PMID[16643054]
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	leaves	n.a.	n.a.	PMID[17125218]
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[17315960]
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	roots	n.a.	n.a.	PMID[17315960]
NPO22421	Microtropis japonica	Species	Celastraceae	Eukaryota	stem	n.a.	n.a.	PMID[18471021]
NPO22421	Microtropis japonica	Species	Celastraceae	Eukaryota	n.a.	stem	n.a.	PMID[18471021]
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18590313]
NPO22421	Microtropis japonica	Species	Celastraceae	Eukaryota	Stems	n.a.	n.a.	PMID[19534471]
NPO22421	Microtropis japonica	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22423	Microtropis fokienensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22421	Microtropis japonica	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22423	Microtropis fokienensis	Species	Celastraceae	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	1
IC50	2

Activity Type	# Activity
Cell line	2
Organism	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	=	36.0	nM	PMID[9784175]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	58.0	nM	PMID[11374943]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	105000.0	nM	DrugMatrix in vitro pharmacology data

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 NPC67777 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	13525
0.1-0.2	34250
0.2-0.3	1479
0.3-0.4	447
0.4-0.5	85
0.5-0.6	35
0.6-0.7	13
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9344	High Similarity	NPC139067
0.9344	High Similarity	NPC177340
0.8871	High Similarity	NPC191082
0.873	High Similarity	NPC43241
0.8281	Intermediate Similarity	NPC4341
0.7778	Intermediate Similarity	NPC270498
0.7727	Intermediate Similarity	NPC479047
0.7727	Intermediate Similarity	NPC291638
0.7681	Intermediate Similarity	NPC184747
0.7463	Intermediate Similarity	NPC246480
0.7333	Intermediate Similarity	NPC75600
0.7333	Intermediate Similarity	NPC483884
0.7231	Intermediate Similarity	NPC473081
0.7231	Intermediate Similarity	NPC200592
0.7231	Intermediate Similarity	NPC610542
0.7143	Intermediate Similarity	NPC479044
0.7042	Intermediate Similarity	NPC266265
0.6957	Remote Similarity	NPC48017
0.6716	Remote Similarity	NPC195647
0.6667	Remote Similarity	NPC92293
0.662	Remote Similarity	NPC147217
0.6528	Remote Similarity	NPC473673
0.6438	Remote Similarity	NPC472574
0.6267	Remote Similarity	NPC70716
0.6267	Remote Similarity	NPC95265
0.6184	Remote Similarity	NPC473613
0.6111	Remote Similarity	NPC17877
0.6087	Remote Similarity	NPC283375
0.6087	Remote Similarity	NPC183122
0.6053	Remote Similarity	NPC97667
0.5974	Remote Similarity	NPC473085
0.5949	Remote Similarity	NPC88593
0.5946	Remote Similarity	NPC137718
0.589	Remote Similarity	NPC51314
0.5811	Remote Similarity	NPC147880
0.5789	Remote Similarity	NPC41481
0.5769	Remote Similarity	NPC473112
0.5769	Remote Similarity	NPC607428
0.575	Remote Similarity	NPC14499
0.5733	Remote Similarity	NPC27377
0.5714	Remote Similarity	NPC479043
0.5696	Remote Similarity	NPC479042
0.5658	Remote Similarity	NPC471100
0.5658	Remote Similarity	NPC605884
0.5634	Remote Similarity	NPC474608
0.5581	Remote Similarity	NPC176413
0.5581	Remote Similarity	NPC483885
0.5526	Remote Similarity	NPC148062
0.5467	Remote Similarity	NPC473060
0.5467	Remote Similarity	NPC163087
0.5455	Remote Similarity	NPC171207
0.5443	Remote Similarity	NPC96903
0.5402	Remote Similarity	NPC294512
0.5357	Remote Similarity	NPC610134
0.527	Remote Similarity	NPC481047
0.527	Remote Similarity	NPC481045
0.5263	Remote Similarity	NPC483902
0.5263	Remote Similarity	NPC472577
0.5256	Remote Similarity	NPC254558
0.5256	Remote Similarity	NPC471107
0.5195	Remote Similarity	NPC483883
0.5195	Remote Similarity	NPC151585
0.5169	Remote Similarity	NPC483868
0.5128	Remote Similarity	NPC270590
0.5056	Remote Similarity	NPC479045

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC67777 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3185
0.1-0.2	5789
0.2-0.3	174
0.3-0.4	2
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