NPASS Compound

Natural Product: NPC319199

Natural Product ID	NPC319199
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VTQWFYXLYNJGCR-VYRIWNHPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	70697811
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 3D 104110 0 0 0 0 0 0 0 0999 V2000 4.4453 3.6301 1.3960 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4699 2.5180 0.9936 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9404 1.1774 1.4419 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6354 0.4903 0.2863 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6071 0.3129 -0.8091 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6973 1.5030 -0.9328 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2423 2.6460 -0.3611 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4450 1.1998 -0.4243 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4417 1.2402 -1.3755 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4995 2.3404 -0.9853 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6564 1.9741 -0.1524 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1820 0.5849 -0.2529 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6990 0.6843 -0.3235 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2073 1.0109 1.0228 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6902 0.8003 1.2257 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0473 -0.5812 0.8415 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4489 -1.0187 0.9331 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7035 -1.8935 -0.3104 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3096 -2.0494 -0.9420 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7469 -0.7198 -0.6235 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3553 -0.4450 -1.0400 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5532 -1.7181 -1.1227 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1564 -1.4816 -1.6466 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7025 -0.0442 -1.5410 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1882 -0.0935 -1.4930 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2019 0.6547 -2.6118 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5754 0.2210 -1.2856 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5176 -0.0720 1.1676 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2274 -0.0094 2.3080 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2118 1.0414 2.2021 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0304 1.3537 3.1018 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1029 1.6302 0.9734 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0650 0.9495 0.2631 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2485 -1.5716 1.6861 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7097 -0.2043 0.9140 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0187 0.3349 1.7566 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8707 -0.8309 -0.6883 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0163 -1.7426 -1.7084 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2363 -0.6813 0.6630 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6036 -0.6877 0.5576 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3383 -0.8822 1.8444 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7861 -0.5618 1.6223 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3595 -1.1470 0.3763 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3648 -1.0978 -0.7470 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1061 -1.5931 -0.3762 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8765 -1.6957 -2.0161 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9423 -1.3818 -3.0293 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8568 -2.4288 0.5795 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9339 0.8294 1.6984 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2465 -2.1863 2.3202 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1501 3.8287 0.5632 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9547 3.3713 2.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9024 4.5905 1.5657 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5328 2.7598 1.5781 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0798 0.5900 1.8177 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6797 1.3531 2.2768 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4465 1.1917 -0.0337 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1887 0.2473 -1.7521 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5612 1.7122 -2.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9247 1.5064 -2.3461 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0826 3.1853 -0.5130 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8872 2.7853 -1.9437 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4749 2.7370 -0.2882 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3485 2.1417 0.9241 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8746 1.6293 -0.9368 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0786 2.1232 1.2349 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6695 0.5518 1.8683 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2327 1.5596 0.6698 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8491 0.8875 2.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5208 -1.8151 1.7781 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1621 -2.8505 -0.0762 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3217 -1.3764 -1.0454 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4302 -2.2234 -2.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7984 -2.9261 -0.5592 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4226 -0.1426 -2.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0636 -2.3421 -1.9218 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5801 -2.3589 -0.2465 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4758 -2.1312 -1.0212 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0216 -1.8324 -2.6895 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1446 -0.5832 -2.4291 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0841 -0.7882 -0.6671 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9957 0.2499 -3.4793 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0490 0.9644 -1.6557 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0916 -0.6534 3.1980 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3859 1.7448 -0.0546 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5979 0.4930 -0.6131 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6897 -1.4441 2.7238 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5192 -2.6019 1.4155 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2034 -1.3495 1.8009 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9309 -1.2459 1.0871 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3637 -2.6118 -1.4753 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0223 -2.1234 -1.8564 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6118 -1.3149 -2.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8978 0.3316 0.1681 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9376 -0.1682 2.5985 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3486 -0.9536 2.5192 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2159 -0.4840 0.0668 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1850 -0.0035 -0.9565 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9763 -2.7865 -2.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8049 -1.1773 -2.2893 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0560 -0.4223 -3.3197 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8417 -2.4125 0.6025 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8158 1.0857 2.6490 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4594 -2.6041 1.8842 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 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 1 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 1 0 23 24 1 0 24 25 1 0 24 26 1 0 20 27 1 0 17 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 16 34 1 0 12 35 1 0 35 36 2 0 5 37 1 0 37 38 1 0 4 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 44 46 1 0 46 47 1 0 43 48 1 0 42 49 1 0 41 50 1 0 7 2 1 0 25 9 1 0 24 12 1 0 21 13 1 0 20 16 1 0 33 28 1 0 45 40 1 0 1 51 1 0 1 52 1 0 1 53 1 0 2 54 1 0 3 55 1 0 3 56 1 0 4 57 1 0 5 58 1 0 6 59 1 0 9 60 1 0 10 61 1 0 10 62 1 0 11 63 1 0 11 64 1 0 13 65 1 0 14 66 1 0 14 67 1 0 15 68 1 0 15 69 1 0 17 70 1 0 18 71 1 0 18 72 1 0 19 73 1 0 19 74 1 0 21 75 1 0 22 76 1 0 22 77 1 0 23 78 1 0 23 79 1 0 25 80 1 0 25 81 1 0 26 82 1 0 27 83 1 0 29 84 1 0 33 85 1 0 33 86 1 0 34 87 1 0 34 88 1 0 34 89 1 0 35 90 1 0 38 91 1 0 38 92 1 0 38 93 1 0 40 94 1 0 41 95 1 0 42 96 1 0 43 97 1 0 44 98 1 0 46 99 1 0 46100 1 0 47101 1 0 48102 1 0 49103 1 0 50104 1 0 M END

Standard InCHIKey	VTQWFYXLYNJGCR-VYRIWNHPSA-N
Standard InCHI	InChI=1S/C36H54O14/c1-18-12-24(49-31-29(42)28(41)27(40)25(15-37)50-31)30(45-3)32(47-18)48-20-4-9-34(17-38)22-5-8-33(2)21(19-13-26(39)46-16-19)7-11-36(33,44)23(22)6-10-35(34,43)14-20/h13,17-18,20-25,27-32,37,40-44H,4-12,14-16H2,1-3H3/t18-,20+,21-,22+,23-,24+,25-,27-,28+,29-,30-,31-,32+,33-,34+,35+,36+/m1/s1
SMILES	CC1CC(C(C(O1)OC2CCC3(C4CCC5(C(CCC5(C4CCC3(C2)O)O)C6=CC(=O)OC6)C)C=O)OC)OC7C(C(C(C(O7)CO)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	710.35	Volume:	686.471 ? Van der Waals volume.
Dense:	1.035	LogP:	-0.412 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.284 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.098 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	39.0
TPSA:	210.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	6.0	Rings:	7.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.113	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.822	Fsp³:	0.889
MCE-18:	135.529 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.006	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.171 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.166	Promiscuous compounds:	0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.031	MDCK Permeability:	-5.184
Pgp-inhibitor:	0.0	Pgp-substrate:	0.991
PAMPA:	1.0 ? 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):	1.0
20% Bioavailability (F20%):	0.882	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.98
Plasma Protein Binding (PPB):	57.173%	Volume Distribution (VD):	-0.416
Fu:	45.37% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.338	BCRP inhibitor:	0.001
BSEP inhibitor:	0.053

ADMET: Metabolism

CYP1A2-inhibitor:	0.041	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.752	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.977	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.808	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.0
HLM stability:	0.0 ? 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):

1.493

Half-life (T1/2):

4.251

ADMET: Toxicity

hERG Blockers:	0.211	hERG Blockers (10um):	0.397
Human Hepatotoxicity (H-HT):	0.811	Drug-induced Liver Injury (DILI):	0.188
AMES Toxicity:	0.947	Rat Oral Acute Toxicity:	0.904
Maximum Recommended Daily Dose:	0.986	Skin Sensitization:	0.847
Carcinogencity:	0.605	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.135
Drug-induced Neurotoxicity:	0.205	Ototoxicity:	0.994
Hematotoxicity:	0.113	Drug-induced Nephrotoxicity:	0.205
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.528
A549 Cytotoxicity:	0.173	Hek293 Cytotoxicity:	0.935
BCF:	0.502 ? 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:	3.593 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.564 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.297 ? 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
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	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

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

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 NPC319199 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	16188
0.1-0.2	28908
0.2-0.3	4090
0.3-0.4	475
0.4-0.5	76
0.5-0.6	65
0.6-0.7	39
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC247190
0.7826	Intermediate Similarity	NPC146857
0.7582	Intermediate Similarity	NPC32793
0.7582	Intermediate Similarity	NPC116075
0.7527	Intermediate Similarity	NPC469749
0.7356	Intermediate Similarity	NPC17896
0.7356	Intermediate Similarity	NPC469755
0.7356	Intermediate Similarity	NPC284406
0.7356	Intermediate Similarity	NPC197707
0.7356	Intermediate Similarity	NPC251866
0.7273	Intermediate Similarity	NPC329675
0.7273	Intermediate Similarity	NPC194716
0.7241	Intermediate Similarity	NPC84987
0.6966	Remote Similarity	NPC6108
0.6966	Remote Similarity	NPC89514
0.6889	Remote Similarity	NPC10823
0.6854	Remote Similarity	NPC219085
0.6771	Remote Similarity	NPC475629
0.6667	Remote Similarity	NPC486138
0.6667	Remote Similarity	NPC276838
0.6531	Remote Similarity	NPC59288
0.6522	Remote Similarity	NPC480914
0.6495	Remote Similarity	NPC475556
0.6495	Remote Similarity	NPC311706
0.6452	Remote Similarity	NPC180079
0.6413	Remote Similarity	NPC157376
0.6413	Remote Similarity	NPC142066
0.6413	Remote Similarity	NPC603972
0.64	Remote Similarity	NPC486146
0.6374	Remote Similarity	NPC99728
0.6374	Remote Similarity	NPC87250
0.6374	Remote Similarity	NPC244402
0.6374	Remote Similarity	NPC50305
0.6238	Remote Similarity	NPC329986
0.6238	Remote Similarity	NPC140092
0.6237	Remote Similarity	NPC5311
0.6237	Remote Similarity	NPC77299
0.6237	Remote Similarity	NPC480906
0.6226	Remote Similarity	NPC486150
0.6162	Remote Similarity	NPC608063
0.6139	Remote Similarity	NPC232785
0.6139	Remote Similarity	NPC486139
0.6061	Remote Similarity	NPC292467
0.6042	Remote Similarity	NPC9499
0.6042	Remote Similarity	NPC471360
0.6042	Remote Similarity	NPC469751
0.6042	Remote Similarity	NPC471361
0.6042	Remote Similarity	NPC86159
0.6042	Remote Similarity	NPC469752
0.6042	Remote Similarity	NPC469754
0.6042	Remote Similarity	NPC70542
0.6	Remote Similarity	NPC188234
0.5981	Remote Similarity	NPC486134
0.5981	Remote Similarity	NPC486141
0.5918	Remote Similarity	NPC480907
0.5914	Remote Similarity	NPC158344
0.5882	Remote Similarity	NPC486143
0.5882	Remote Similarity	NPC125077
0.5882	Remote Similarity	NPC486135
0.5882	Remote Similarity	NPC486142
0.5882	Remote Similarity	NPC486137
0.5882	Remote Similarity	NPC486149
0.5849	Remote Similarity	NPC329636
0.5842	Remote Similarity	NPC480910
0.5842	Remote Similarity	NPC480909
0.5833	Remote Similarity	NPC243196
0.58	Remote Similarity	NPC30483
0.58	Remote Similarity	NPC470897
0.5784	Remote Similarity	NPC264336
0.5773	Remote Similarity	NPC146456
0.5743	Remote Similarity	NPC236973
0.5743	Remote Similarity	NPC32177
0.5743	Remote Similarity	NPC469756
0.5743	Remote Similarity	NPC275901
0.5729	Remote Similarity	NPC469750
0.5686	Remote Similarity	NPC240070
0.567	Remote Similarity	NPC76572
0.567	Remote Similarity	NPC193382
0.566	Remote Similarity	NPC476221
0.566	Remote Similarity	NPC477709
0.5657	Remote Similarity	NPC469753
0.5631	Remote Similarity	NPC486127
0.5631	Remote Similarity	NPC610296
0.5625	Remote Similarity	NPC309034
0.5596	Remote Similarity	NPC475419
0.5579	Remote Similarity	NPC474418
0.5567	Remote Similarity	NPC34390
0.5556	Remote Similarity	NPC471359
0.5556	Remote Similarity	NPC486144
0.5556	Remote Similarity	NPC486145
0.5556	Remote Similarity	NPC486147
0.5556	Remote Similarity	NPC486136
0.5556	Remote Similarity	NPC486148
0.5534	Remote Similarity	NPC486130
0.5521	Remote Similarity	NPC99620
0.5455	Remote Similarity	NPC77319
0.5455	Remote Similarity	NPC120390
0.5455	Remote Similarity	NPC471351
0.5455	Remote Similarity	NPC471355
0.5398	Remote Similarity	NPC474423
0.5393	Remote Similarity	NPC72772
0.5347	Remote Similarity	NPC471354
0.5347	Remote Similarity	NPC27507
0.5321	Remote Similarity	NPC486128
0.5321	Remote Similarity	NPC488938
0.5321	Remote Similarity	NPC488937
0.5315	Remote Similarity	NPC74259
0.5273	Remote Similarity	NPC475590
0.5268	Remote Similarity	NPC474908
0.5253	Remote Similarity	NPC480915
0.5248	Remote Similarity	NPC93883
0.5229	Remote Similarity	NPC486132
0.5229	Remote Similarity	NPC486131
0.5221	Remote Similarity	NPC329784
0.5149	Remote Similarity	NPC250556
0.5133	Remote Similarity	NPC486140
0.5098	Remote Similarity	NPC305574

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319199 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6210
0.1-0.2	2849
0.2-0.3	72
0.3-0.4	10
0.4-0.5	5
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.7356	Intermediate Similarity	NPD7319	Approved
0.5149	Remote Similarity	NPD7507	Pre-clinical

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